Design and synthesis of bioactive compounds containing thiazolidine and thiazolidinone derivatives

Abstract

Stochastic optimisation model of oil refinery industry and uncertainty quantification in scenario tree of pricing and demandThiazolidine and thiazolidinone derivatives are important heterocyclic compounds which have varying biological activity in humans and have been shown to be effective against a variety of pathogens such as antimicrobial, antifungal, antioxidant, anti-inflammatory, anticancer, antidiabetic and anti-HIV. This study consists of three series of heterocyclic thiazolidine and thiazolidinone derivatives which have been synthesized from low to excellent yields. The first step in this study is to prepare a series of 2-(substituted phenyl)-thiazolidine-4-carboxylic acid and its derivatives in one step reaction of L-cysteine with different substituted of benzaldehyde in ethanol and water (3:1) to obtain sixteen compounds (28%-92%). All compounds were evaluated for their antifungal activity against Candida albicans and Aspergillus niger, using fluconazole as a reference drug. The assay revealed that, compound 172k showed significant activity (14 mm ZOI, 64 µg/mL IC50 and 15 mm ZOI, > 32 µg/mL IC50) against C. albicans and A. niger, respectively. The issue of the high adaptability of HIV to the introduced drugs, as the retrovirus can easily mutate its active site has widely spread the interest of scientists to discover new compounds as candidate for the disease. Up to date, there is no commercial drug on HIV that contains thiazolidinone yet and there are a few previous researches that showed the high potential of the derivatives as drug candidates for anti-HIV. Thus, this study proposes the development of a novel HIV-1 RT drug based on the thiazolidinone chemical structure. The docking studies facilitated the identification of crucial interactions between the HIV-1 RT enzyme and thiazolidin-4-one inhibitors. The binding energy for new targeted second series of 2-(4-hydroxy-3-methoxyphenyl)-3-phenethylthiazolidin-4-one and their derivatives (194-216) displayed strong binding energy values (binding energy of -10.54 to -9.07 kcal/mol). In addition, nine new compounds for the third series of 2-(4-hydroxy-3-methoxyphenyl)-3-(pyridin-2-yl)-1,3-thiazolidin-4-one and their derivatives show moderate to strong binding energy values (binding energy of -9.14 to -8.40 kcal/mol). All compounds for the second series (176-192) and the third series (194-216) gave better activity than the standard drug (Efavirenz), which binding energy for the drug was (-8.30 kcal/mol). In the second and third series of the synthesized compounds, several thiazolidinone derivatives were produced by cyclization reaction using vanillin, mercaptoacetic acid and aromatic amine in the presence of toluene to form new 2,3-diaryl-1,3-thiazolidin-4-one derivatives. The second series of 2-(4-hydroxy-3-methoxyphenyl)-3-phenethylthiazolidin-4-one and its derivatives were synthesized by reflux of reaction of the starting materials consisting of the amine and five groups (fluoro, chloro, bromo, nitro and methoxy), attached at ortho, meta and para position of 2-phenylethylamine ring with vanillin and thioacetic acid in the presence of dry toluene to obtain twelve new compounds (24%-89%). In the same way, the third series was synthesized by reacting vanillin, mercaptoacetic acid and 2-aminopyridine and two groups (chloro and methyl) attached at 3-,4-,5- and 6-position of 2-aminopyridine ring to obtain nine new compounds of 2-(4-hydroxy-3-methoxy-phenyl)-3-(pyridin-2-yl)-1,3-thiazolidin-4-ones and its derivatives (45%-75%). All the synthesized compounds were confirmed by FTIR, 1H NMR, 13C NMR and MS.