Investigation of Structure, Reactivity, and Biological Activity of Thiazole-Containing Compounds: A Computational Study
DOI:
https://doi.org/10.29356/jmcs.v70i1.2378Keywords:
Thiazole, density functional theory, molecular docking, anticancer, anticholinesterase reactivityAbstract
Abstract. Herein, the structure, stability, reactivity, and biological activity of recently synthesized thiazole-containing compounds are evaluated using density functional theory (DFT), molecular docking, and molecular dynamics (MD) techniques. All the selected thiazole-containing compounds are optimized using DFT (B3LYP/def2-TZVPP) method. The DFT reactivity parameters such as energy gap, chemical hardness, chemical potential, ionization potential, electron affinity, electronegativity, softness, and electrophilicity index are calculated. Our calculations indicate that the thiazole-containing compound M1 shows significant structural stability and reactivity. Our physicochemical and pharmacokinetic studies suggest that the selected thiazole-containing compounds possess a drug-like nature. The antibacterial, anticancer, anticholinergic, and antifungal activity of the selected thiazole-containing compounds are investigated using molecular docking and dynamics methods. Our docking studies revealed that M1 shows higher binding affinity with the selected protein targets, which confirms their biological activity. Similarly, M6, M9, and M10 possess lesser binding energy among the selected thiazole-containing compounds. Our MD simulations show that the ligand M1 strongly interacts with the 1M17 protein. shows higher binding affinity with the selected protein targets, which confirms their biological activity. Similarly, M6, M9, and M10 possess lesser binding energy among the selected thiazole-containing compounds. Our MD simulations show that the ligand M1 strongly interacts with the 1M17 protein. This is further evidence that the ligand M1 is a promising candidate for the development of new drugs against deadly pathogens.
Resumen. En este trabajo, se evalúan la estructura, estabilidad, reactividad y actividad biológica de compuestos que contienen tiazol recientemente sintetizados mediante la teoría del funcional de la densidad (DFT), acoplamiento molecular y técnicas de dinámica molecular (MD). Todos los compuestos seleccionados que contienen tiazol se optimizan mediante el método DFT B3LYP/def2-TZVPP. Se calculan los parámetros de reactividad de la DFT, como la brecha de energía, la dureza química, el potencial químico, el potencial de ionización, la afinidad electrónica, la electronegatividad, la suavidad y el índice de electrofilicidad. Nuestros cálculos indican que el compuesto M1, que contiene tiazol, muestra una estabilidad estructural y una reactividad significativas. Nuestros estudios fisicoquímicos y farmacocinéticos sugieren que los compuestos que contienen tiazol seleccionados poseen una naturaleza similar a la de un fármaco. Se investiga la actividad antibacteriana, anticancerígena, anticolinérgica y antifúngica de los compuestos que contienen tiazol seleccionados mediante métodos de acoplamiento molecular y de dinámica. Nuestros estudios de acoplamiento revelaron que M1 presenta una mayor afinidad de unión con las proteínas diana seleccionadas, lo que confirma su actividad biológica. De igual manera, M6, M9 y M10 poseen una menor energía de unión entre los compuestos que contienen los tiazoles seleccionados. Nuestras simulaciones muestran que el ligando M1 interactúa de forma fuerte con la proteína 1M17. Esto constituye una prueba más de que el ligando M1 es un candidato prometedor para el desarrollo de nuevos fármacos contra patógenos mortales.
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