Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the mos... more Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-prod...
The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit comp... more The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory...
Pistacia lentiscus L. (Anacardiaceae) is widely distributed in the Mediterranean basin. Its fruit... more Pistacia lentiscus L. (Anacardiaceae) is widely distributed in the Mediterranean basin. Its fruit oil is used in traditional medicine to treat burns, skin impairments as well as inflammatory diseases as soothing massage or internal use. An increased interest is spotted lately with several commercial brands are spun portraying the benefits of this oil but with no stringent regulations to ascertain its safe use as an edible or cosmeceutical product. This work concerned the investigation of secondary metabolites presents in Pistacia lentiscus fruits oil using both GC-MS and HPLC-DAD-MS technics, and the evaluation of cytotoxicity on human normal dermal fibroblasts to assess safety of use as cosmetic ingredient. This study stands as the first one to report the identification of alkylsalicylic acids in fruits oil and unsaponifiable fraction of Pistacia lentiscus fruit oil which calls for therefore, quantification of alkylsalicylic acids, known as skin irritants, in Pistacia lentiscus oil...
Structure elucidation of unknown compounds has been the task of natural products chemists for a l... more Structure elucidation of unknown compounds has been the task of natural products chemists for a long time and their approach seems to be the most efficient when it comes to identification. Very recently, Kokkotou et al. proposed a work-flow based on an integrative approach for new metabolite identification. This approach, including prediction of 2D NMR HSQC spectra, demonstrated the necessity for implementation of new algorithms leading to the prediction of 2D NMR spectra. Herein we present a method based on both quantum mechanics (QM) and Hierarchical Organisation of Spherical Environments (HOSE) of the prediction 2D NMR spectra.
A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomim... more A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.
Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly us... more Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the b...
Journal of Pharmaceutical and Biomedical Analysis, 2021
Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in tradi... more Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in traditional medicine all over tropical areas, especially in Brazil, to relieve inflammation-associated symptoms. Flavonol glycosides with unusual sugar moiety are among the major metabolites. Nevertheless, there are not enough quality control studies that can contribute to authentication of B. pinnatum and determination of their markers. As it is also used as medicinal plant in several countries, it is necessary to provide data related to safety, efficacy and quality. In this context, this work aims to isolate the major flavonoids from B. pinnatum hydroethanolic extract, to validate a method to quantify the content of chemical markers and to evaluate their xanthine oxidase inhibition and antioxidant activity. The extract was submitted to centrifugal partition chromatography (CPC). The solvents system CyHex-EtOAc-EtOH-H 2 O, 0.5:9:3:5.5, v/v/v/v was selected by shake-flask method. Four flavonoids (quercetin 3-O-␣-L-arabinopyranosyl-(1→2)-O-␣-L-rhamnopyranoside (1), kaempferol 3-O-␣-L-arabinopyranosyl-(1→2)-O-␣-L-rhamnopyranoside (2), quercetin 3-O-␣-L-rhamnopyranoside (3) and kaempferol 3-O-␣-L-rhamnopyranoside (4)) were isolated in a single and fast CPC run and their structures were confirmed by NMR analysis. An UPLC-DAD quantification method was established for the first time with validation of required parameters, according to RDC 166/2017. The calibration curves were linear with correlation coefficient ranging from 0.9996 to 0.9997 while the values of LOD (0.0077-1.984 ng.mL −1), LOQ (0.0263-6.012 ng.mL −1), recovery (≥ 80.7 %) and inter-day (%RSD ≤ 3.581) and intra-day precision (%RSD ≤ 2.628) were satisfactory. Quantitative analysis of these compounds showed that the proportion of 1, 2 and 3 were 2.43, 0.25 and 0.33 % (24.3 mg.g −1 , 0.25 mg.g −1 and 0.33 mg.g −1 of extract), respectively. Moreover, in vitro xanthine oxidase (XO), DPPH and ABTS inhibition were evaluated for the extract and the major flavonoids. Compounds 2 (168 M) and 3 (124 M) moderately inhibited XO, while compounds 1 and 3 displayed average radical scavenging activity. In conclusion, our results suggest the flavonoid 1 as a specific marker which may be used for quality control of B. pinnatum hydroethanolic leaves extract.
Until now, tuberculosis is always a dangerous infectious disease. Because of the enlargement of m... more Until now, tuberculosis is always a dangerous infectious disease. Because of the enlargement of multidrug-resistant strains (MDR-TB), the need of new drugs becomes more important. Fusing of 2 pharmacophores (phenothiazine and benzopyran), we intend to synthesize some new pyranophenothiazine derivatives, and evaluate their antituberculosis activities. The designed compounds were prepared using conventional synthetic methods with all PA chemical agents (from Merk, TCI, Sigma). The structure of all synthesized compounds had been confirmed by analysis of NMR and MS spectra. Antimycobacterial activity of the synthesized compounds on Mycobacterium bovis BCG (or on the virulent strain Mycobacterium tuberculosis H37Rv for the most promising compounds) had been determined using the Microdilution resazurin assay. 2 compounds 8 and 9 were obtained by Claisen rearrangement of intermediate dimethylpropargyl ether. The sulfoxide and (+)cis-diol sulfoxide derivatives were obtained by oxydation, and the dihydro-derivatives-by reduction of the leader compounds. The anti-tuberculosis activities of 12 synthesized compounds were evaluated. Only the leading compound of linear structure (pyrano[b]phenothiazine) and 2 non-sulfoxide derivatives of angular structure (pyrano[a]phenothiazine) exhibited a mild inhibiting activity on the tested tuberculosis source. 12 new pyrano-phenothiazine compounds have been prepared and bioevaluated. The results showed that 3 compounds exhibited a mild inhibiting activity on the tested tuberculosis source. These structural requirements will be taken into account for the design of further analogues in pyranophenothiazine series.
A chemically stable fluorescent mimic of dihydroartemisinin, artemether and arteether with conser... more A chemically stable fluorescent mimic of dihydroartemisinin, artemether and arteether with conserved bioactivity and specificity shows high pharmacological relevance to the antimalarial drugs
Tuberculosis is a dangerous infectious disease. Because of the enlargement of multidrug-resistant... more Tuberculosis is a dangerous infectious disease. Because of the enlargement of multidrug-resistant strains (MDR-TB), the need of new drugs becomes more important. In the last research, 2 pyranophenothiazine series had been synthesized and bioevaluated. Herein, eight N-substituted pyranophenothiazine derivatives from 2 series were designed, synthesized and evaluated for their antituberculosis activities. The designed compounds were prepared by alkylation reactions and all synthesized compounds were confirmed by analysis of NMR and MS spectra. Antimycobacterial activity of the synthesized compounds on Mycobacterium bovis BCG had been determined using the microdilution resazurin assay-The results showed that 4 compounds exhibited a mild inhibiting activity on the tested tuberculosis strains. These structural requirements will be taken into account for the design of further analogues in pyranophenothiazine series.
The objective is to develop a natural cosmetic ingredient from Eryngium maritimum regarding the h... more The objective is to develop a natural cosmetic ingredient from Eryngium maritimum regarding the high interest of consumer in these ingredients for cosmetic use. METHODS: Five eco-friendly techniques of extraction were applied to Eryngium maritimum aerial parts among conventional reflux extraction (with green solvent) and alternative techniques (supercritical fluid extraction (SFE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and ultrasound combined with microwave extraction (UAE + MAE)). Several criteria were evaluated to allow the optimal choice for an industrialized ingredient: yield of extraction, chemical composition and biological activities such as antimicrobial, antioxidant, anti-collagenase and anti-tyrosinase activities. The extracts were analysed by liquid chromatography mass spectrometry (LC-HRMS), and the hierarchical Pearson classification (HCA) allowed to highlight the group of metabolites preferably extracted depending on the technique of extraction used. RESULTS: The biological results highlight that SFE and 80% ethanol reflux extracts have the best responses to biological activities such as antimicrobial, depigmenting and antioxidant activities, followed by water reflux extraction. Their activities might be due to the presence of different groups of metabolites favourably extracted by these techniques. CONCLUSION: Among these extractions, water reflux extraction provided the optimal results considering the compromise between extraction yield and biological activities for the development of a cosmetic ingredient. pr ef erentielle de certains groupes de m etabolites extraits plus favorablement par ces techniques. CONCLUSION: Parmi les extractions test ees, l'extraction par reflux a l'eau (proc ed e respectueux de l'environnement) d'Eryngium maritimum, fournit le meilleur compromis en termes d'efficacit es biologiques plurielles, de rendement d'extraction et de productivit e/ consommation energ etique, pour le d eveloppement d'un ingr edient cosm etique 'ecofriendly'.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for tre... more Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass...
Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is describe... more Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC 50 of 3.0 ± 1.0 µM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC 50 of 1.5 ± 1 µM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4.
Influence of the stereoisomeric position of the reactive acetate groups of the benzo[b]acronycine... more Influence of the stereoisomeric position of the reactive acetate groups of the benzo[b]acronycine derivative S23906-1 on its DNA alkylation, helix opening, cytotoxic and anti-tumor activities.
Spirokermeline, a new macrocyclic compound derived from resorcinol, was isolated from Kermadecia ... more Spirokermeline, a new macrocyclic compound derived from resorcinol, was isolated from Kermadecia elliptica, an endemic species of New Caledonia. The structure of spirokermeline was elucidated on the basis of spectroscopic analysis and X‐ray single‐crystal diffraction analysis. This is the first time that a 3H,3′H‐spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione was isolated from higher plants and only the second time that this scaffold was found in nature. A possible biosynthetic pathway is proposed.
Chemical study of the aerial parts of Anthospermum emirnense led to the isolation of one original... more Chemical study of the aerial parts of Anthospermum emirnense led to the isolation of one original iridoid glycoside (1) along with six known iridoids (2–7), three lignans (8–10), two flavonoids (11–12), one coumarin (13), two anthraquinones (14–15), two benzoic acids (16–17) and three triterpenoids (18–20). These results are the first chemical data on non-volatile constituents of this genus. The chemotaxonomic significance of these compounds is discussed.
Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the mos... more Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-prod...
The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit comp... more The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory...
Pistacia lentiscus L. (Anacardiaceae) is widely distributed in the Mediterranean basin. Its fruit... more Pistacia lentiscus L. (Anacardiaceae) is widely distributed in the Mediterranean basin. Its fruit oil is used in traditional medicine to treat burns, skin impairments as well as inflammatory diseases as soothing massage or internal use. An increased interest is spotted lately with several commercial brands are spun portraying the benefits of this oil but with no stringent regulations to ascertain its safe use as an edible or cosmeceutical product. This work concerned the investigation of secondary metabolites presents in Pistacia lentiscus fruits oil using both GC-MS and HPLC-DAD-MS technics, and the evaluation of cytotoxicity on human normal dermal fibroblasts to assess safety of use as cosmetic ingredient. This study stands as the first one to report the identification of alkylsalicylic acids in fruits oil and unsaponifiable fraction of Pistacia lentiscus fruit oil which calls for therefore, quantification of alkylsalicylic acids, known as skin irritants, in Pistacia lentiscus oil...
Structure elucidation of unknown compounds has been the task of natural products chemists for a l... more Structure elucidation of unknown compounds has been the task of natural products chemists for a long time and their approach seems to be the most efficient when it comes to identification. Very recently, Kokkotou et al. proposed a work-flow based on an integrative approach for new metabolite identification. This approach, including prediction of 2D NMR HSQC spectra, demonstrated the necessity for implementation of new algorithms leading to the prediction of 2D NMR spectra. Herein we present a method based on both quantum mechanics (QM) and Hierarchical Organisation of Spherical Environments (HOSE) of the prediction 2D NMR spectra.
A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomim... more A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV 50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV 50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.
Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly us... more Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the b...
Journal of Pharmaceutical and Biomedical Analysis, 2021
Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in tradi... more Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is widely used as leaf juice or extracts in traditional medicine all over tropical areas, especially in Brazil, to relieve inflammation-associated symptoms. Flavonol glycosides with unusual sugar moiety are among the major metabolites. Nevertheless, there are not enough quality control studies that can contribute to authentication of B. pinnatum and determination of their markers. As it is also used as medicinal plant in several countries, it is necessary to provide data related to safety, efficacy and quality. In this context, this work aims to isolate the major flavonoids from B. pinnatum hydroethanolic extract, to validate a method to quantify the content of chemical markers and to evaluate their xanthine oxidase inhibition and antioxidant activity. The extract was submitted to centrifugal partition chromatography (CPC). The solvents system CyHex-EtOAc-EtOH-H 2 O, 0.5:9:3:5.5, v/v/v/v was selected by shake-flask method. Four flavonoids (quercetin 3-O-␣-L-arabinopyranosyl-(1→2)-O-␣-L-rhamnopyranoside (1), kaempferol 3-O-␣-L-arabinopyranosyl-(1→2)-O-␣-L-rhamnopyranoside (2), quercetin 3-O-␣-L-rhamnopyranoside (3) and kaempferol 3-O-␣-L-rhamnopyranoside (4)) were isolated in a single and fast CPC run and their structures were confirmed by NMR analysis. An UPLC-DAD quantification method was established for the first time with validation of required parameters, according to RDC 166/2017. The calibration curves were linear with correlation coefficient ranging from 0.9996 to 0.9997 while the values of LOD (0.0077-1.984 ng.mL −1), LOQ (0.0263-6.012 ng.mL −1), recovery (≥ 80.7 %) and inter-day (%RSD ≤ 3.581) and intra-day precision (%RSD ≤ 2.628) were satisfactory. Quantitative analysis of these compounds showed that the proportion of 1, 2 and 3 were 2.43, 0.25 and 0.33 % (24.3 mg.g −1 , 0.25 mg.g −1 and 0.33 mg.g −1 of extract), respectively. Moreover, in vitro xanthine oxidase (XO), DPPH and ABTS inhibition were evaluated for the extract and the major flavonoids. Compounds 2 (168 M) and 3 (124 M) moderately inhibited XO, while compounds 1 and 3 displayed average radical scavenging activity. In conclusion, our results suggest the flavonoid 1 as a specific marker which may be used for quality control of B. pinnatum hydroethanolic leaves extract.
Until now, tuberculosis is always a dangerous infectious disease. Because of the enlargement of m... more Until now, tuberculosis is always a dangerous infectious disease. Because of the enlargement of multidrug-resistant strains (MDR-TB), the need of new drugs becomes more important. Fusing of 2 pharmacophores (phenothiazine and benzopyran), we intend to synthesize some new pyranophenothiazine derivatives, and evaluate their antituberculosis activities. The designed compounds were prepared using conventional synthetic methods with all PA chemical agents (from Merk, TCI, Sigma). The structure of all synthesized compounds had been confirmed by analysis of NMR and MS spectra. Antimycobacterial activity of the synthesized compounds on Mycobacterium bovis BCG (or on the virulent strain Mycobacterium tuberculosis H37Rv for the most promising compounds) had been determined using the Microdilution resazurin assay. 2 compounds 8 and 9 were obtained by Claisen rearrangement of intermediate dimethylpropargyl ether. The sulfoxide and (+)cis-diol sulfoxide derivatives were obtained by oxydation, and the dihydro-derivatives-by reduction of the leader compounds. The anti-tuberculosis activities of 12 synthesized compounds were evaluated. Only the leading compound of linear structure (pyrano[b]phenothiazine) and 2 non-sulfoxide derivatives of angular structure (pyrano[a]phenothiazine) exhibited a mild inhibiting activity on the tested tuberculosis source. 12 new pyrano-phenothiazine compounds have been prepared and bioevaluated. The results showed that 3 compounds exhibited a mild inhibiting activity on the tested tuberculosis source. These structural requirements will be taken into account for the design of further analogues in pyranophenothiazine series.
A chemically stable fluorescent mimic of dihydroartemisinin, artemether and arteether with conser... more A chemically stable fluorescent mimic of dihydroartemisinin, artemether and arteether with conserved bioactivity and specificity shows high pharmacological relevance to the antimalarial drugs
Tuberculosis is a dangerous infectious disease. Because of the enlargement of multidrug-resistant... more Tuberculosis is a dangerous infectious disease. Because of the enlargement of multidrug-resistant strains (MDR-TB), the need of new drugs becomes more important. In the last research, 2 pyranophenothiazine series had been synthesized and bioevaluated. Herein, eight N-substituted pyranophenothiazine derivatives from 2 series were designed, synthesized and evaluated for their antituberculosis activities. The designed compounds were prepared by alkylation reactions and all synthesized compounds were confirmed by analysis of NMR and MS spectra. Antimycobacterial activity of the synthesized compounds on Mycobacterium bovis BCG had been determined using the microdilution resazurin assay-The results showed that 4 compounds exhibited a mild inhibiting activity on the tested tuberculosis strains. These structural requirements will be taken into account for the design of further analogues in pyranophenothiazine series.
The objective is to develop a natural cosmetic ingredient from Eryngium maritimum regarding the h... more The objective is to develop a natural cosmetic ingredient from Eryngium maritimum regarding the high interest of consumer in these ingredients for cosmetic use. METHODS: Five eco-friendly techniques of extraction were applied to Eryngium maritimum aerial parts among conventional reflux extraction (with green solvent) and alternative techniques (supercritical fluid extraction (SFE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and ultrasound combined with microwave extraction (UAE + MAE)). Several criteria were evaluated to allow the optimal choice for an industrialized ingredient: yield of extraction, chemical composition and biological activities such as antimicrobial, antioxidant, anti-collagenase and anti-tyrosinase activities. The extracts were analysed by liquid chromatography mass spectrometry (LC-HRMS), and the hierarchical Pearson classification (HCA) allowed to highlight the group of metabolites preferably extracted depending on the technique of extraction used. RESULTS: The biological results highlight that SFE and 80% ethanol reflux extracts have the best responses to biological activities such as antimicrobial, depigmenting and antioxidant activities, followed by water reflux extraction. Their activities might be due to the presence of different groups of metabolites favourably extracted by these techniques. CONCLUSION: Among these extractions, water reflux extraction provided the optimal results considering the compromise between extraction yield and biological activities for the development of a cosmetic ingredient. pr ef erentielle de certains groupes de m etabolites extraits plus favorablement par ces techniques. CONCLUSION: Parmi les extractions test ees, l'extraction par reflux a l'eau (proc ed e respectueux de l'environnement) d'Eryngium maritimum, fournit le meilleur compromis en termes d'efficacit es biologiques plurielles, de rendement d'extraction et de productivit e/ consommation energ etique, pour le d eveloppement d'un ingr edient cosm etique 'ecofriendly'.
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for tre... more Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass...
Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is describe... more Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC 50 of 3.0 ± 1.0 µM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC 50 of 1.5 ± 1 µM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4.
Influence of the stereoisomeric position of the reactive acetate groups of the benzo[b]acronycine... more Influence of the stereoisomeric position of the reactive acetate groups of the benzo[b]acronycine derivative S23906-1 on its DNA alkylation, helix opening, cytotoxic and anti-tumor activities.
Spirokermeline, a new macrocyclic compound derived from resorcinol, was isolated from Kermadecia ... more Spirokermeline, a new macrocyclic compound derived from resorcinol, was isolated from Kermadecia elliptica, an endemic species of New Caledonia. The structure of spirokermeline was elucidated on the basis of spectroscopic analysis and X‐ray single‐crystal diffraction analysis. This is the first time that a 3H,3′H‐spiro[benzofuran‐2,1′‐isobenzofuran]‐3,3′‐dione was isolated from higher plants and only the second time that this scaffold was found in nature. A possible biosynthetic pathway is proposed.
Chemical study of the aerial parts of Anthospermum emirnense led to the isolation of one original... more Chemical study of the aerial parts of Anthospermum emirnense led to the isolation of one original iridoid glycoside (1) along with six known iridoids (2–7), three lignans (8–10), two flavonoids (11–12), one coumarin (13), two anthraquinones (14–15), two benzoic acids (16–17) and three triterpenoids (18–20). These results are the first chemical data on non-volatile constituents of this genus. The chemotaxonomic significance of these compounds is discussed.
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