Transport protein interaction and target pathway analysis of a hybrid antifungal compound synthesized by linking triazolothiadiazine ring system with the pyridine ring

The present manuscript explores the serum albumin interaction and target pathway analysis of a newly developed antifungal agent, 7-[2-(4-chlorophenyl) hydrazinylidene]-6-methyl-3-(pyridin-4-yl)-7H-[1, 2, 4]triazolo[3,4-b][1, 3, 4]thiadiazine (5E). Candida species are among the leading causes of systemic fungal infections, highlighting a need for new effective antifungal therapies because of drug resistance and associated side effects with existing treatment regimens. The synthesized compound (5E) demonstrated superior antifungal characteristics in comparison to ketaconazole, suggesting potential for more effective therapeutic options. Serum albumins in plasma binds and carries molecules, including drugs. Spectroscopic techniques, computational methods and target pathway analysis were employed for studying BSA-5E interactions. The compound 5E quenched BSA fluorescence via static quenching. The 5E primarily interacts with the IIA and IIIA subdomains of BSA which was aided by hydrogen binding. The target prediction tool of SwissADME predicted kinases, particularly CDK5R1, CDK5, PLK1, FLT1, KDR, and NTRK1, to be the most significant targets of 5E, followed by enzymes including lyases and oxidoreductases. GeneMANIA analysis identified key kinase-regulating lyases and oxidoreductase for carrying out antifungal action. The associated miRNAs were depicted by MIENTURNET providing insights into its pharmacokinetics and therapeutic potential at molecular level. Molecular docking aided to comprehend the BSA-5E interaction at protein level.