Novel pyridine and 1,3,4-oxadiazole-linked 1,3-thiazole hybrids: Synthesis, anticancer evaluation, and computational insights
Year: 2025
Type: article
Abstract: In medicinal chemistry and natural products, heterocyclic compounds have been thoroughly explored because of their impressive pharmacological properties. Thiazole-based heterocycles are frequently utilized in synthetic chemistry and drug design and have various biological activities. To discover new cytotoxic agents with promising efficacy against breast cancer, novel pyridine and 1,3,4-oxadiazole-linked 1,3-thiazole hybrids were synthesized via Hantzsch thiazole synthesis reaction between thioamide and various α-haloketones, with good yields. The synthesized 1,3-thiazole hybrids were subjected to analytical characterization via various spectroscopic techniques, including 1H NMR, 13C NMR, FTIR, and mass spectrometry. The compounds were then evaluated for their in vitro anticancer activity against the MCF-7 breast cancer cell line using the SRB assay, with doxorubicin and cisplatin as reference standards. The results revealed that compound 7a (IC50 = 28.51 ± 1.70 µM), which features a methyl substituent at the para position of a phenyl ring, exhibited significant activity. In contrast, the presence of electron-withdrawing groups (EWGs) diminished the activity. Furthermore, a detailed structure‒activity relationship (SAR) study was performed. A series of computational analyses, including docking studies to predict the orientation of the compounds within the binding site, molecular dynamics (MD) simulations to assess the stability of the compounds, thermal MMGBSA analysis to evaluate the binding energy, DFT studies to determine the energy gap of frontier molecular orbitals, and in silico drug-likeness assessments to analyze the pharmacokinetic profiles of the 1,3-thiazole hybrids, were conducted.
Source: Journal of Molecular Structure
Authors: Manjunath R, Padmapriya M, Samyak Pandey, Raksha Nayak, K Sreedhara Ranganath Pai, Santosh L Gaonkar
Institution: Manipal Academy of Higher Education
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,360
OpenAlex ID: W4415327195