Metelytsia L. In silico and in vitro evaluation of azole derivatives antimicrobial activity against resistant strains of fungal and bacterial cultures

Synthetic derivatives of oxazole, thiazole and imidazole. Study of biologically active azoles as novel antimicrobial agents against clinical fluconazole-resistant strains of Candida spp. and antibiotic-resistant bacterial strains S. aureus and M. tuberculosis by in silico and in vitro methods. QSAR prediction, molecular docking, in vitro microbiological testing methods. New QSAR models have been created to predict the antimicrobial activity of 2,4,5-substituted 1,3-oxazole derivatives, 1,3-substituted imidazolium salts, oxazole-containing triphenylphosphonium salts and thiazole-containing isoniazid derivatives with high predictive ability, which are located and available on the ОСНЕМ server and can be used by other scientists to searching, analyzing and predicting of activity of the corresponding series of heterocyclic compounds against resistant clinical strains of microbials. The inhibitory activity of N-dodecyl imidazolium derivatives both against the human laryngeal carcinoma Hep-2 cells culture and against fluconazole-resistant strains of Candida spp. is experimentally established. It has been demonstrated that antimicotic activity of 5-alkylsulfanyl-1,3-oxazol-4-yltriphenylphosphonium salts against Candida spp. fluconazole-resistant strains is determined by the nature of the substituents at position 5 of the oxazole ring. A number of novel thiazole-containing isoniazid derivatives active against the multi-resistant HRv strain M. tuberculosis have been identified using the created QSAR models of a wide range of M. tuberculosis inhibitors and based on the results of experimental studies. The high antimicrobial potential of 1,3-dialkyl substituted imidazolium and 5-alkylthio-1,3-oxazol-4-yltriphenylphosphonium salts as antibacterials agents the antibiotic-resistant clinical strain S. aureus is demonstrated by in silico and in vitro methods. The field of use is bioorganic chemistry.