Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

Abstract

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS ) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (–8.4 and –9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.

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

“…[6] Coumarins, a part of the flavonoid group of plant secondary metabolite, are a wide class of natural and synthetic compounds that showed versatile biological and pharmacological activities. [7][8][9][10][11][12][13][14] Many scientific reports unveiled that natural and synthetic coumarin are drawn considerable attention in medicinal chemistry. [15,16] The great attention paid by researchers to the study of coumarin derivatives is explained by their broad spectrum of biological activities including antiinflammatory, [17] antidiabetic, antiAlzheimer, anticancer, antioxidant, Anticonvulscent, antituberculosis, and as inhibitors of SARS-CoV-2 (COVID-19) virus.…”

“…Coumarin, 2 H ‐1‐benzopyran‐2‐one moiety is a bicyclic heterocycle consisting of benzene and 2‐ pyrone rings [6] . Coumarins, a part of the flavonoid group of plant secondary metabolite, are a wide class of natural and synthetic compounds that showed versatile biological and pharmacological activities [7–14] . Many scientific reports unveiled that natural and synthetic coumarin are drawn considerable attention in medicinal chemistry [15,16] .…”

Novel Thiadiazole-Based Molecules as Promising Inhibitors of Black Fungi and Pathogenic Bacteria: In Vitro Antimicrobial Evaluation and Molecular Docking Studies

“…The N atom has a unique nature that gives flexibility to the biological targets. Accordingly, N -heterocyclic compounds have many therapeutic uses as scaffolds for new drug candidates [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In the medicinal chemistry, pyrazine, pyrazoline, indazole, and thiazole derivatives, for example, could offer a broad spectrum of therapeutic and pharmacological applications [ 31 ].…”

“…In the medicinal chemistry, pyrazine, pyrazoline, indazole, and thiazole derivatives, for example, could offer a broad spectrum of therapeutic and pharmacological applications [ 31 ]. 1,3,4-thiadiazoles are of great interest due to their significant importance for investigating potent bioactive compounds with a wide range of applications in the pharmaceutical industry [ 15 , 16 , 32 , 33 , 34 , 35 , 36 , 37 ]…”

In silico study to identify novel potential thiadiazole-based molecules as anti-Covid-19 candidates by hierarchical virtual screening and molecular dynamics simulations

“…On the other hand, 1,3,4-thiadiazole moieties have been reported for their pharmaceutical properties. Many antiviral drugs like acetazolamide, besaglybuzole (glybuzole), and furidiazine (triafur) were reported to append the 1,3,4-thiadiazole in their constructors [9][10][11][12][13].…”