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

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.

4-Methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin

“…Contrary to coumarin and thiadiazole derivatives, compounds combining both structural subunits in a common molecule are relatively poorly studied. Nevertheless, several examples have shown a wide spectrum of biological activities, including antimicrobial [43], antifungal [44,45], anticancer [46,47], for the treatment of Alzheimer's disease and neurodegenerative disorders [48], suppressing allergic reactions agents [49], and many others.…”

Spectroscopic characterization and assessment of microbiological potential of 1,3,4-thiadiazole derivative showing ESIPT dual fluorescence enhanced by aggregation effects

“…Recently, searching for new agents with antifungal activity has become more important because of the increase in frequency of severe fungal infections and the expansion of fungal resistance to drugs 4 . Selected derivatives from the group of 1,3,4-thiadiazoles prove potentially beneficial effects in the treatment and prevention of said diseases 5,6 , and some of them have already found clinical applications 7,8 . Their unusual spectroscopic and crystallographic properties dictate a large spectrum of their additional applications; they can be used as laser pigments 9 , ligands complexing rare earth metal ions 10 , molecular probes 11 , as well as UV stabilizers 12 .…”

Design, synthetic approach,in silicomolecular docking and antibacterial activity of quinazolin-2,4-dione hybrids bearing bioactive scaffolds

“…They were cultivated in Mueller Hinton broth at 35 ± 2 °C for 24 h. The antimicrobial activity and MIC were performed as reported by Qader et al (2021). 2,27–36…”