Synthesis, structural studies, cytotoxicity and computational evaluation of 1,3,4-oxadiazolyl-thio-oxazines as potential NF-κB inhibitors in breast cancer

Narasimhachar, Bhanuprakash C. and Harish, Keshav Kumar and Nagaraja, Omantheswara and Vishwanath, Divakar and Chandrashekar, H. B. and Mamatha, S. K. and Mahendra, M. and Lobie, Peter E. and Rangappa, K. S. and Basappa, Basappa and Chandrashekara, P. G. (2026) Synthesis, structural studies, cytotoxicity and computational evaluation of 1,3,4-oxadiazolyl-thio-oxazines as potential NF-κB inhibitors in breast cancer. Journal of Molecular Structure, 1353. p. 144494. ISSN 1872-8014

Text (Full Text) Synthesis, structural studie.pdf - Published Version Download (2MB)

Abstract

In this study, eleven 1,3,4-oxadiazolyl-thio-oxazines (4a–4k) were synthesized and characterized using ¹H/¹³C NMR, IR spectroscopy, and mass spectrometry. Single-crystal XRD confirmed that 4c crystallized in the mono- clinic P2 ₁/n space group, revealing key intermolecular interactions through Hirshfeld surface analyses. DFT studies using the B3LYP/6–311++G(d,p) basis set optimized all the compounds without imaginary frequencies. Frontier molecular orbital analysis provided HOMO–LUMO gaps and global reactivity descriptors, whereas MEP surface analysis offered insights into the charge distribution and potential intermolecular interactions of the optimized structures. For all compounds, the key structural identity of the thiomethylene bond was confirmed by ¹H NMR doublets (3.5–4.5 ppm) from diastereotopic coupling near N&S and ¹³C signals (25–40 ppm) indicating sulfur deshielding. The oxadiazole and oxazine rings were validated by C=N (1563–1613 cm⁻¹) and C–O–C (1144–1201 cm⁻¹) absorptions, with IR confirming C–S (696–713 cm⁻¹) and S–CH₂ (~1400 cm⁻¹) linkages. Mass spectra gave [M + H]⁺ ions as expected, with halogenated derivatives showing predicted isotopic patterns. Furthermore, the theoretical and experimental ¹H and ¹³C NMR data were in agreement, as supported by the correlation coefficient and RMSD values. Alamar Blue assay on MCF-7 breast cancer cells identified 4c (IC₅₀ = 33.06 μM) and 4g (IC₅₀ = 21.24 μM) as active candidates. It was validated with molecular docking and 100 ns MD simulations, confirming 4g’s strong binding affinity towards NF-κB p65 ( 8.1 kcal/mol) via stable hydrogen bonds and hydrophobic contacts.

Item Type:	Article
Uncontrolled Keywords:	1,3,4-oxadiazolyl thio-oxazines, Single-crystal x-ray diffraction, Density functional theory, NF-κB inhibition, Molecular docking, Molecular dynamics simulation
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	C Swapna Library Assistant
Date Deposited:	17 Dec 2025 04:59
Last Modified:	17 Dec 2025 04:59
URI:	http://eprints.uni-mysore.ac.in/id/eprint/18212

Actions (login required)

View Item