A NEW SERIES OF TETRAZOLE-HYDRAZONE HYBRIDS ENDOWED WITH ANTICANDIDAL ACTIVITY

EFMC-ASMC International Symposium on Advances in Synthetic and Medicinal Chemistry, Zagreb, Hırvatistan, 3 - 07 Eylül 2023, ss.271

Hydrazones occupy a prominent place in the development of novel drugs for the treatment of several diseases,

particularly bacterial and fungal infections due to their unique structural features such as carrying hydrogen bond

donor and acceptor groups allowing these ligands to interact with key residues of crucial biological targets.1

Besides, tetrazole, the bioisoster of carboxylic acid, is one of the most important five-membered heterocycles

and its derivatives have been reported to show diverse biological activities including antifungal activity.2

In an attempt to identify potent anticandidal agents, herein new tetrazole-hydrazone hybrids were synthesized

efficiently. All compounds were examined for their anticandidal activities using a broth microdilution assay and

minimum inhibitory concentration (MIC) was determined for each compound. Compounds 1 and 3 (Fig. 1) were

found to be as effective as tioconazole (MIC= 50 μM) on Candida krusei (ATCC® 6258TM) and Candida

parapsilosis (ATCC® 22019TM) with a MIC value of 50 μM. MTT assay was performed to evaluate their

cytotoxic effects on NIH/3T3 mouse embryonic fibroblast cells. These compounds did not show cytotoxicity on

NIH/3T3 cells at the tested concentrations indicating that the anticandidal effects of both compounds were

selective. The pharmacokinetic profiles of compounds 1 and 3 were predicted by means of QikProp, a predictive

Absorption, Distribution, Metabolism and Excretion (ADME) module within the Maestro suite produced by

Schrödinger. According to Lipinski's rule of five and Jorgensen's rule of three, both compounds were found to

possess favorable drug-likeness and oral bioavailability. In vitro and in silico studies pointed out the potential of

compounds 1 and 3 as promising candidates for the treatment of candidiasis.