Synthesis of Small Molecule Library of Novel Nicotinamide Derivatives as Anticancer Agents and Computational Screening

A small molecule library of nicotinamide derivatives synthesized and characterized their structure by interpretation of ¹H NMR, ¹³C NMR, and Mass spectral data. The new molecules were screened for their in vitro anticancer activity against human breast (MCF-7) and cervical (HeLa) cell lines by using Doxorubicin as standard reference. Pyridine linked nicotinamide derivatives displayed potent activity against both the cell lines. The trifluoromethyl substituted pyridine analogue demonstrated outstanding activity with IC₅₀ value of 8.70 ± 0.23 µM and 8.97 ± 0.31 µM against MCF-7 and HeLa cell lines respectively, with respect to Doxorubicin IC₅₀ value of 9.06 ± 0.36 µM (MCF-7) and 9.17 ± 0.39 µM (HeLa). The compound 6 with thiomethyl group displayed activity with IC₅₀ value of 9.01 ± 0.38 µM and 9.82 ± 0.41 µM against MCF-7 and HeLa cell lines correspondingly. The methyl substituted compound 5h displayed encouraging activity with IC₅₀ value of 10.47 ± 0.41 µM (MCF-7) and 11.87 ± 0.45 µM (HeLa). Molecular docking study performed using potent molecules 5h , 5i, and 6 against estrogen receptor alpha (PDB ID: 3ERT), obtained highest docking score value for ligand 5i (9.5 kcal/mol). The predicted ADME of compounds indicated their drug-like characteristics.