RESUMO
From a medical point of view lot of existing antibiotics became unusable because microbial gained strong antibiotic resistance. The combination of two compounds in one core may lead to kill such type of pathogens. Herein, we developed pyranopyrazole derivatives comprising benzoxazole moiety by green approach strategy and studied their antimicrobial performance on four bacteria and two fungi. As a result, most of the compounds delivered reliable toxicity to kill the pathogens. In those,6aexhibited considerable activity against the microbial pathogens. Moreover,compounds 6d, 6l,and6nshowed prominent antibacterial activity. In addition, molecular docking studies of docked compounds revealed the strong bonding interaction with DNA-Gyrase and were docked into the intercalation location of DNA of the DNA-gyrase complex. The molecule bounded to the DNA stabilized by the H bonds, hydrophobic interactions, and π-π interaction. In addition, the linked 5-chlorobenazoxazole structure stabilized by the DT-8 and DG2009 of the F chain with pi-pi interactions. From the computer-aided results, it was observed that compound6a demonstrated maximum docking score -10.0 kcal/mole towards DNA-gyrase. Overall, this investigation suggested that these biologically active compounds can be utilized as leads for preclinical studies with the goal of developing newer antimicrobial drugs.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzoxazóis/química , Benzoxazóis/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Anti-Infecciosos/síntese química , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Benzoxazóis/síntese química , DNA Girase/metabolismo , Desenho de Fármacos , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Fungos/efeitos dos fármacos , Fungos/enzimologia , Química Verde , Humanos , Simulação de Acoplamento Molecular , Micoses/tratamento farmacológico , Micoses/microbiologia , Pirazóis/síntese química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologiaRESUMO
Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy.