An article Synthesis, Antimicrobial Evaluation and Molecular Docking of Some Potential 2,6-disubstituted 1H-Benzimidazoles; Non-Classical Antifolates WOS:000489963500010 published article about DIHYDROFOLATE-REDUCTASE INHIBITORS; ONE-POT PREPARATION; 2-SUBSTITUTED BENZIMIDAZOLES; BIOLOGICAL EVALUATION; SELECTIVE INHIBITORS; DHFR INHIBITORS; DESIGN; DERIVATIVES; RESISTANT in [Harer, Sunil] Savitribai Phule Pune Univ, Sharadchandra Pawar Coll Pharm, Fac Pharmaceut Sci, Dept Pharmaceut Chem, Pune 412409, Maharashtra, India; [Bhatia, Manish; Kawade, Vikram] Shivaji Univ, Bharati Vidyapeeth Coll Pharm, Fac Pharmaceut Sci, Dept Pharmaceut Chem, Kolhapur, Maharashtra, India in 2019.0, Cited 49.0. Recommanded Product: 4′-Hydroxyacetophenone. The Name is 4′-Hydroxyacetophenone. Through research, I have a further understanding and discovery of 99-93-4
Background: Dihydrofolate reductase is one of the important enzymes for thymidylate and purine synthesis in micro-organisms. A large number of drugs have been designed to inhibit microbial DHFR but over the period of time some drugs have developed resistance and cross reactivity towards the enzyme. Over the past few decades, benzimidazoles, triazoles and their derivatives have been grabbing the attention of the synthetic chemists for their wide gamut of antibacterial and antifungal activities targeting microbial protein DHFR. Objective: Our goal behind present investigation is to explore benzimidazoles class of drugs as microbial DHFR inhibitors by studying ligand-receptor binding interactions, in vitro enzyme inhibition assay and confirmation of anti-microbial activity against selected pathogenic micro-organisms. Method: A library containing thirty novel 2,6-disubstituted 1H-benzimidazoles was synthesized by one pot condensation of o-nitro aniline or 2,4-dinitro aniline with series of aldehydes or acetophenones using Na2S2O4 or SnCl2 respectively and reflux for 5-6hr. Structures of compounds have been confirmed by spectroscopic methods as 1H and C-13 NMR, FT-IR and MS. In vitro DHFR inhibition study was performed by using Epoch microplate reader and IC50 of the test compounds was compared with Trimethoprim. In vitro antimicrobial activity was performed against selected clinical pathogens by agar disk diffusion method and MIC (mu g/mL) was reported. Results: Moderate to good level of DHFR inhibition was observed with IC50 values in the range of 7-23 mu M. Compounds B1, B19, B22, B24 and B30 has expressed 1.1 to 1.4 folds more prominent DHFR inhibitory activity as compared to standard Trimethoprim. Remarkable antimicrobial activity was exhibited by B1, B19, B22, B24 and B30. Molecular docking study has revealed perfect binding of test ligands with key amino acids of DHFR as Phe31, Ile94, Ile5, Asp27, Gln32 and Phe36. Conclusion: Nature of 1H-benzimidazole substituents at position 2 and 6 had influence over magnitude and type of molecular binding and variation in the biological activity. Present series of 1H-benzimidazoles could be considered promising broad-spectrum antimicrobial candidates that deserve in future for preclinical antimicrobial evaluation and development of newer antimicrobial agents targeting microbial DHFR.
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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles