Synthesis, antimicrobial activity and 3D-QSAR study of novel 5-substituted-1,3,4-thiadiazole Schiff base derivatives

• Published in: Journal of molecular structure 2022-11, Vol.1267, p.133629, Article 133629
• Main Authors: Lou, Jiayu, Wang, Huashan, Wang, Sanyan, Han, Junjun, Wang, Meiyi
• Format: Article
• Language: English
• Subjects: 1,3,4-Thiadiazole; 3D-QSAR; Inhibitory activity; Schiff base
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133629

•Inhibitory activity of some compounds surpasses that of commercial fungicides.•The compounds were studied by QSAR for inhibition of aspergillus niger activity.•QSAR models were used to predict compounds with bacterial inhibitory ability. In this study, 21 new thiadiazole Schiff base derivatives were synthesized based on the reactive group splicing principle, and the structures of the target compounds were confirmed and characterized by 1H NMR, FT-IR and HRMS. The inhibition activity of the compounds was tested in vitro against Escherichia coli, Staphylococcus aureus, Aspergillus niger, Rhizopus, Penicillium, Botrytis cinerea and Alternaria using mycelial growth rate method. The results showed that most of the compounds exhibited good biological activity at a dose of 50 µg/mL. Among them, compounds 2b, 2r, and 2a exhibited inhibition rates against the tested microbe comparable to that of the control drug Chlorothalonil. A preliminary three-dimensional quantitative conformational relationship (3D-QSAR) study of the inhibitory activity of the target compounds against Aspergillus niger was carried out using CoMFA and CoMSIA, and the model results showed that increasing the volume of the 2- and 6-positions of benzene ring A and the 3-position substituent of benzene ring B, decreasing the volume of the 5-position substituent benzene ring A; increasing hydrophobic groups at the 6-position of benzene ring A and the 2′-position of benzene ring B; increasing the 3′-position hydrogen bond donor group and decreasing the 3′-position hydrogen bond acceptor group of benzene ring B can improve the biological activity of the compounds. The inhibitory activity of the compounds can be improved.