Armand Gellis

Original quinazoline derivatives displaying antiplasmodial properties.

The multistep synthesis of new quinazoline-derived molecules and their in vitro antiplasmodial evaluation on the W2 chloroquino-resistant Plasmodium falciparum strain is described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward two human cell lines (K652 and HepG2) in order to calculate their respective selectivity indexes (S.I.). Among the fourteen tested molecules, two exhibited both significant antiplasmodial activity (IC(50)=0.95 and 1.3 microM) and low toxicity (IC(50)>100 or 125 microM), compared with two reference drugs: chloroquine and doxycycline. The structure activity relationships establish that the molecular scaffold which exerts the best profile is the 6-nitro-2-(tosylmethyl)-N-(3-substituted-phenyl)-quinazolin-4-amine. The hit molecules were finally investigated regarding their potential action toward two other protozoa, Leishmania donovani and Toxoplasma gondii, showing that these molecules display a selective antiplasmodial activity.

Microwave-assisted synthesis in aqueous medium of new quinazoline derivatives as anticancer agent precursors

Fast and eco-friendly microwave-irradiated reactions permitting the “green synthesis” of new 2-substituted quinazoline derivatives in aqueous medium via S-alkylation or SRN1 reaction from 2-chloromethyl-3-methylquinazolin-4(3H)-one derivatives with different benzenesulfinic acids and nitronate anions, are reported herein.

Synthesis and cytotoxicity evaluation of some benzimidazole-4,7-diones as bioreductive anticancer agents

New benzimidazole-4,7-diones substituted at 2-position were synthesized via a microwave-assisted reaction using 2-chloromethyl-1,5,6-trimethyl-1H-benzimidazole-4,7-dione 5b as a key intermediate compound. Their cytotoxicity has been evaluated on colon, breast and lung cancer cell lines. The dimer 17 was shown to possess excellent cytotoxicity comparable to that of mitomycin C.

SYNTHESE ET REACTIONS SRN1 EN SERIE 5-NITROTHIAZOLE

A new heterocyclic reductive alkylating agent, the 2-methyl-4-chloromethyl-5-nitrothiazole, has been synthesized and could react with the 2-nitropropane anion as nucleophile, to give the 2-methyl-4-(2-methylpropenyl)-5-nitrothiazole as the major product. The reaction was shown to proceed by the SRN1 mechanism which was confirmed by the classical criteria for SRN1 reaction: the leaving group effect, the electronwithdrawing group effect and classical inhibition experiments by dioxygen, p-dinitrobenzene, cupric chloride or di-tert-butylnitroxide. This reaction has been extended to nitrocyclopentane and nitrocyclohexane anions with lower yields.

Electron transfer reactivity in 5-nitrouracil series☆

Abstract The sodium salt of 1,3,6-trimethyl-5-nitrouracil is shown to react with various reductive alkylating agents such as p-nitrobenzyl chloride and dinitropropane by an S RN 1 mechanism to give new potentially bioactive 5-nitrouracil derivatives. 1,3-Dimethyl-5-nitro-6-chloromethyluracil also reacts by an S RN 1 mechanism with 2-nitropropane anion to afford a new uracil derivative bearing a trisubstituted ethylenic double bond at the 6-position.

Rapid microwave-promoted synthesis of new sulfonylmethylbenzothiazoles in water

A simple, fast and inexpensive microwave-irradiated reaction permitting the synthesis of new sulfonylmethylbenzothiazoles in water by S-alkylation of 2-chloromethyl-6-nitrobenzothiazole 2 with different benzenesulfinic acid anions 3 is reported.

Efficient synthesis of new 6-nitrobenzothiazoles using microwave irradiation

2-Chloromethyl-6-nitrobenzothiazole 2 is obtained by cyclocondensation of 2-aminobenzenethiol and chloroacetic acid. This product allows the synthesis of 2-alkyl-6-nitrobenzothiazoles 5, 17-24 under microwave activation via an electron transfer reaction by successive C-alkylation of nitronate anions 3, 6-13 and nitrous acid elimination.

Fast electron transfer C-alkylation of 2-nitropropane anion under microwave irradiation

Microwave irradiation is shown to be an attractive methodology for fast electron transfer C-alkylation reactions of 2-nitropropane anion by different reductive alkylating agents. This method is simple, rapid and affords excellent C-alkylation yields.

RAPID SYNTHESIS OF SUBSTITUTED IMIDAZO[2,1-b]THIAZOLES UNDER MICROWAVE CONDITIONS

A simple, rapid, and efficient method for the synthesis of original substituted imidazo[2,1-b]thiazoles under microwave irradiation is described.

Les réactions de transfert monoélectronique : de l’électron au médicament

Resume Les etudes sur les reactions de transfert d’electron ont connu, depuis 1954 avec les premiers travaux de H. Taube (prix Nobel de chimie 1983) et de R. Marcus (prix Nobel de chimie 1991), un developpement considerable en chimie inorganique, organique et biologique. En chimie organique, un nouveau type de reaction de substitution en chaine faisant intervenir des especes paramagnetiques a ete defini et identifie sous le sigle S RN 1 (Substitution radicalaire nucleophile unimoleculaire). En choisissant des molecules plus ou moins complexes possedant des motifs structuraux (groupement electron-accepteur et site(s) d’alkylation) convenablement disposes, notre groupe de recherche a etendu ce concept en serie heterocyclique (S RN 1 HET) et quinonique (S RN 1 QUI). Ces etudes ont permis la preparation, dans des conditions douces, de molecules hautement ramifiees, difficilement accessibles par d’autres voies de synthese et possedant des activites pharmacologiques elevees dans differents domaines. Nous avons ainsi decouvert de nouveaux mecanismes reactionnels comme la LD-S RN 1 (S RN 1 a Longue Distance), l’E RC 1 (Elimination Radicalaire en Chaine unimoleculaire), la bis-S RN 1 et la poly-S RN 1. Parallelement, nous avons developpe de nouvelles methodologies utilisant les micro-ondes ce qui nous a permis de renforcer l’attrait des reactions de transfert monoelectronique en chimie pharmaceutique pour l’obtention de « candidats-medicaments ».