Investigation of Novel Mucorales Fungal Inhibitors: Synthesis, In‐Silico Study and Anti‐Fungal Potency of Novel Class of Coumarin‐6‐Sulfonamides‐Thiazole and Thiadiazole Hybrids
Ahmed Sabt, Mohamad T. Abdelrahman, Mohamed Abdelraof, Huda R. M. Rashdan
Abstract
Abstract A series of coumarin‐6‐sulfonamides derivatives bearing a thiazole and thiadiazole scaffold were synthesized, their chemical structures were inferred from correct spectral and microanalytical data. All the newly synthesized compounds have been screened for their ability to prevent the proliferation of Mucor racemosus , Syncephalastrum racemosum in vitro. The most potent compounds were chosen to determine the MIC value in compared to the standard antifungal agent (Posaconazole). Remarkably, an excellent anti‐mucormycosis was obtained by compounds known as 8 d , and 8 d with MIC value close to that observed by the standard Posaconazole. Amolecular. Docking study was performed where compounds 3 , 5 a , 5 d , 8 d , 8 e , 10 c and 10 e were docked against the fungal enzyme sterol 14‐alpha demethylase (CYP51) “PDB id: 5FSA”. In silico, compounds 8 d & 8 e showed the best docking by forming 3H bonds and free binding energy (12.2 & 12 K cal/mol) close to the binding energy (12.2 K cal/mol) of the co‐crystalized inhibitor (posconazol. From wet lab and dry lab results, one can recommend compounds 8 d & 8 e for further antifungal drug development.