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

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.

[1]  Huda R. M. Rashdan,et al.  Synthesis, Identification, Computer-Aided Docking Studies, and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents , 2021, Molecules.

[2]  S. Szafert,et al.  Solvent-Free C-H Alkynylation of Azulenes , 2021, Organic Chemistry Frontiers.

[3]  Ihsan A. Shehadi,et al.  Antibacterial Activities and Molecular Docking of Novel Sulfone Biscompound Containing Bioactive 1,2,3-Triazole Moiety , 2021, Molecules.

[4]  M. Abdel-Naby,et al.  Kinetic, Catalytic and Thermodynamic Properties of Immobilized Milk Clotting Enzyme on Activated Chitosan Polymer and its Application in Cheese Making , 2021 .

[5]  Ihsan A. Shehadi,et al.  Lysozyme and Human Serum Albumin Proteins as Potential Nitric Oxide Cardiovascular Drug Carriers: Theoretical and Experimental Investigation. , 2021, The journal of physical chemistry. B.

[6]  V. Poroikov,et al.  Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies , 2021, Antibiotics.

[7]  M. Moustafa,et al.  Polyphenolic extracts from pomegranate and watermelon wastes as substrate to fabricate sustainable silver nanoparticles with larvicidal effect against Spodoptera littoralis , 2021, Saudi journal of biological sciences.

[8]  Abdulilah Ece,et al.  Design, synthesis, characterization, in vitro and in silico evaluation of novel imidazo[2,1-b][1,3,4]thiadiazoles as highly potent acetylcholinesterase and non-classical carbonic anhydrase inhibitors. , 2021, Bioorganic chemistry.

[9]  M. Suchard,et al.  Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil , 2021, Science.

[10]  H. Piao,et al.  Synthesis and Antimicrobial Activity Evaluation of Imidazole‐Fused Imidazo[2,1‐b][1,3,4]thiadiazole Analogues , 2021, ChemMedChem.

[11]  M. Fadel,et al.  Cellulases and animal feed production by solid-state fermentation by Aspergillus fumigatus NRCF-122 mutant , 2021 .

[12]  Huda R. M. Rashdan,et al.  Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents , 2021, Molecules.

[13]  R. Fernández-Lafuente,et al.  Solvent-free esterifications mediated by immobilized lipases: a review from thermodynamic and kinetic perspectives , 2021, Catalysis Science & Technology.

[14]  Ihsan A. Shehadi,et al.  Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-b]Thiazole Linked Thiadiazole Conjugates , 2020, Molecules.

[15]  A. Abu‐Hashem.  Synthesis and antimicrobial activity of new 1,2,4‐triazole, 1,3,4‐oxadiazole, 1,3,4‐thiadiazole, thiopyrane, thiazolidinone, and azepine derivatives , 2020 .

[16]  Ihsan A. Shehadi,et al.  Physicochemical stability study of protein–benzoic acid complexes using molecular dynamics simulations , 2020, Amino Acids.

[17]  Huda R. M. Rashdan,et al.  New Potent 5α- Reductase and Aromatase Inhibitors Derived from 1,2,3-Triazole Derivative , 2020, Molecules.

[18]  M. Abdelraof,et al.  Green synthesis of bacterial cellulose/bioactive glass nanocomposites: Effect of glass nanoparticles on cellulose yield, biocompatibility and antimicrobial activity. , 2019, International journal of biological macromolecules.

[19]  M. Arooj,et al.  Characterisation of the protein-facilitated ion-transfer mechanism at a polarised aqueous-organic interface. , 2019, The journal of physical chemistry. B.

[20]  Huda R. M. Rashdan,et al.  Synthesis and Biological Evaluation of Some New Pyridines, Isoxazoles and Isoxazolopyridazines Bearing 1,2,3-Triazole Moiety , 2019, Acta Poloniae Pharmaceutica - Drug Research.

[21]  Huda R. M. Rashdan,et al.  Toward Rational Design of Novel Anti-Cancer Drugs Based on Targeting, Solubility, and Bioavailability Exemplified by 1,3,4-Thiadiazole Derivatives Synthesized Under Solvent-Free Conditions , 2019, Molecules.

[22]  Huda R. M. Rashdan,et al.  Synthesis, Antimicrobial and Antitumor Evaluations of a New Class of Thiazoles Substituted on the Chromene Scaffold. , 2019, Mini reviews in medicinal chemistry.

[23]  Huda R. M. Rashdan,et al.  Eco-friendly one-pot synthesis of some new pyrazolo[1,2-b]phthalazinediones with antiproliferative efficacy on human hepatic cancer cell lines , 2018 .

[24]  Tamer T. El-Idreesy,et al.  Green One‐Pot Solvent‐Free Synthesis of Pyrazolo[1,5‐a]pyrimidines, Azolo[3,4‐d]pyridiazines, and Thieno[2,3‐b]pyridines Containing Triazole Moiety , 2016 .

[25]  Berk Hess,et al.  GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers , 2015 .

[26]  Xuefu You,et al.  Identification of an anti-TB compound targeting the tyrosyl-tRNA synthetase. , 2015, The Journal of antimicrobial chemotherapy.

[27]  S. Sherif,et al.  Synthesis of some new antimicrobial 5,6,7,8- tetrahydropyrimido[4,5-b]quinolone derivatives , 2014 .

[28]  F. Bărbuceanu,et al.  New heterocyclic compounds from 1,2,4-triazole and 1,3,4-thiadiazole class bearing diphenylsulfone moieties. Synthesis, characterization and antimicrobial activity evaluation. , 2012, European journal of medicinal chemistry.

[29]  H. S. Hussein,et al.  Influence of selective media on successful detection of Shiga toxin-producing Escherichia coli in food, fecal, and environmental samples. , 2008, Foodborne pathogens and disease.

[30]  D. Doğruer,et al.  Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives. , 2008, Journal of enzyme inhibition and medicinal chemistry.

[31]  A. Pui,et al.  Synthesis and antimicrobial activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds having a D,L-methionine moiety. , 2007, Molecules.

[32]  K. Kawasaki,et al.  Synthesis and biological activities of benzofuran antifungal agents targeting fungal N-myristoyltransferase. , 2003, Bioorganic & medicinal chemistry.

[33]  M. Mirzaei,et al.  Synthesis and antibacterial activity of some novel N-substituted piperazinyl-quinolones. , 2001, Bollettino chimico farmaceutico.