RESUMO
Tuberculosis remains a global health threat, with increasing infection rates and mortality despite existing anti-TB drugs. The present work focuses on the research findings regarding the development and evaluation of thiadiazole-linked thiazole derivatives as potential anti-tuberculosis agents. We present the synthesis data and confirm the compound structures using spectroscopic techniques. The current study reports twelve thiazole-thiadiazole compounds (5 a-5 l) for their anti-tuberculosis and related bioactivities. This paper emphasizes compounds 5 g, 5 i, and 5 l, which exhibited promising MIC values, leading to further in silico and interaction analysis. Pharmacophore mapping data included in the present analysis identified tubercular ThyX as potential drug targets. The compounds were evaluated for anti-tubercular activity using standard methods, revealing significant MIC values, particularly compound 5 l, with the best MIC value of 7.1285â µg/ml. Compounds 5 g and 5 i also demonstrated moderate to good MIC values against M.â tuberculosis (H37Ra). Structural inspection of the docked poses revealed interactions such as hydrogen bonds, halogen bonds, and interactions containing Pi electron cloud, shedding light on conserved interactions with residues like Argâ 95, Cysâ 43, Hisâ 69, and Argâ 87 from the tubercular ThyX enzyme.
Assuntos
Antituberculosos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Mycobacterium tuberculosis , Tiadiazóis , Tiazóis , Antituberculosos/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Tiadiazóis/química , Tiadiazóis/farmacologia , Tiadiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia , Tiazóis/síntese química , Mycobacterium tuberculosis/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , HumanosRESUMO
In an attempt to develop potent anti-cancer agents, a new 1,3,4-substituted-thiadiazole derivatives (8b-g), starting from 4-substituted-thiazol-2-chloroacetamides (4b-g), were synthesized and evaluated for their cytotoxic effects on multiple human cancer cell lines, including the hepatocellular carcinoma (HEPG-2), human lung carcinoma (A549), human breast carcinoma (MCF-7) and pseudo-normal human embryonic liver (L02) cancer cell lines by an MTT assay. Among all synthesized compounds, compound 8d showed the potent anti-cancer activities with GI50 values of 2.98, 2.85 and 2.53 µM against MCF-7, A549 and HepG-2 cell lines respectively as compared to standard drug Doxorubicin. Furthermore, molecular modelling studies have spotlighted the anchoring role of 1,3,4-substituted-thiadiazole moiety in bonding and hydrophobic interaction with the key amino acid residues. Therefore, these results can provide promising starting points for further development of best anti-cancer agents.