Synthesis of Thiazole Derivatives and Evaluation of Their Antiamoebic Activity and Cytotoxicity

Abstract

Five ethyl 5-alkyl-2-amino-1,3-thiazol-4-yl acetates designated compounds 4a-e incorporating octyl, decyl, dodecyl, tetradecyl, and hexadecyl alkyl chains, respectively, were prepared by reacting 4-alkyl-4-bromo-3-oxobutyric acid ethyl esters 3a-e with thiourea in dried acetonitrile. Compounds 3a-e were synthesized by reacting alkylated ethyl acetoacetates with bromine. The newly synthesized compounds were characterized by mass spectrometry, NMR, and elemental analysis. Compounds 4a-c demonstrated good in vitro antiamoebic activity against Acanthamoeba polyphaga exposed to 10 mg L 1 for 6 h at 28 . Compound 4b showed the highest antiamoebic activity among the tested compounds, comparable to that of chlorhexidine dihydrochloride CHX , decreasing the number of viable cells to below the detection limit of 1 cell mL 1 . The activity of compounds 4a and 4c was similar to that of the commercial antifungal agent fluconazole Flu . The cytotoxic and hemolytic activity of the compounds was assayed against human neonate dermal fibroblasts and sheep erythrocytes, respectively. Compounds 4a-c were less cytotoxic than Flu and CHX. Our results suggest that compound 4b, which is composed of a 2-amino-thiazole attached to a decyl group and an ethyl ester moiety, is a particularly safe and effective alternative amoebicidal agent.

Applications of medicinal chemistry for drug discovery against Acanthamoeba infections

“…These compounds showed less cytotoxicity as compared to commercially available drugs. The results proposed that compound 20 is safer than other three compounds, indicating it as a useful drug candidate 80 …”

“…Shirai et al, 80 stated that biguanide disinfectants are normally used in the solutions of contact lens. They concentrated on the development of novel antiamoebic agents, which have a low molecular weight and show more antiamoebic activity as compared to biguanide disinfectants.…”

“…The results proposed that compound 20 is safer than other three compounds, indicating it as a useful drug candidate. 80…”

Novel Tetrazoles against Acanthamoeba castellanii Belonging to the T4 Genotype

“…The medicinal utility of synthetic azole classes has shown tremendous value against Acanthamoeba. The azole subclasses which have shown anti-Acanthamoeba activity previously include benzimidazole, thiazole, benzotriazole, benzothiazole, imidazole, and tetrazole [8][9][10][11][12]. Recently, we have reported that synthetic quinazolinones possess potent anti-amoebic activities against Acanthamoeba [13,14].…”