2-hydrazinobenzothiazole based derivatives: Synthesis, characterization, antifungal, DNA binding and molecular modelling approaches

• Published in: Journal of molecular structure 2024-07, Vol.1308, p.138051, Article 138051
• Main Authors: Nouman, Rana, Manish, Ahmedi, Saiema, Mehandi, Rabiya, Ahmad, Shaban, Fatima, Tuba, Raza, Khalid, Manzoor, Nikhat, Rahisuddin
• Format: Article
• Language: English
• Subjects: Antifungal; Benzothiozole derivatives; DNA binding; Molecular modelling study
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.138051

•Synthesis, experimental spectral characterization of synthesized compounds.•Evaluation of antifungal activity, DNA binding.•The molecular modeling study also carried out of lead compounds. In this study, eleven new 2-hydrazinobenzothizole derivatives (Z1–Z11) were synthesized by condensation reaction. The molecular structure of the derivatives was confirmed using FT-IR, NMR, and mass spectrometry. The heterocyclic derivatives (Z1–Z11) were tested for their in vitro antifungal activity against the fungal strains C. albicans, C. glabrata, and C. tropicalis. The outcomes showed that heterocyclic analog Z5, with a MIC value of 450μM, demonstrates noteworthy activity against strain C. tropicalis, while Z7 displays antifungal activity against C. tropicalis, with MIC values of 480μM. When compared to the common medication fluconazole. Ct-DNA binding studies of both lead compounds were carried out using UV–visible, fluorescence, and cyclic voltammetry (CV) measurements. Results from the binding study depicted that the compounds demonstrated a groove mode of binding. In addition, molecular docking analysis of the ligand molecules with PDBID: 5FSA revealed numerous interactions, strong binding, and a high MM/GBSA score, indicating a stable complex. Furthermore, a 100ns molecular dynamics (MD) simulation demonstrated minimal deviation and fluctuations, along with significant intermolecular interactions, further confirming the stability of the complex. [Display omitted]