From Synthesis to Simulation: A Thiadiazole Scaffold With Predicted COX-2 Binding and Distinct Electronic Properties
ChemistrySelect, cilt.11, sa.39, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 11 Sayı: 39
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/slct.74886
- Dergi Adı: ChemistrySelect
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Academic Search Ultimate (EBSCO)
- Anahtar Kelimeler: ADME, DFT, docking, hirshfeld surface analysis, molecular, predicted COX-2 binding, single-crystal XRD
- Hacettepe Üniversitesi Adresli: Evet
Özet
In this study, we report the synthesis of a novel heterocyclic molecule (6) containing an imino-1,3,4-thiadiazole ring connected to benzamide, together with its structural and computational investigation. The compound was characterized by NMR, HRMS, and single-crystal x-ray diffraction (SC-XRD), and crystals suitable for diffraction were obtained by slow evaporation from ethanol. Hirshfeld surface analysis identified the principal noncovalent contacts governing crystal packing. Density functional theory (DFT) calculations were used to examine the optimized molecular geometry, frontier orbitals, molecular electrostatic potential (MESP), dipole moment, and global reactivity descriptors, and the calculated geometry was compared with the SC-XRD structure. Molecular docking against COX-2, using co-crystallized celecoxib as a structural reference, generated a plausible binding pose, while MM-GBSA and residue-wise RMSF analysis provided model-dependent energetic and conformational descriptors. SwissADME was used only to estimate physicochemical properties, drug-likeness, and pharmacokinetic tendencies. The computational results support compound 6 as a candidate scaffold for further investigation, but COX-2 inhibitory potency, selectivity, and pharmacokinetic performance require experimental validation.