Structure-based design and synthesis of (E)-l-(s-pheny1)-N-(4-(2,2,4-trimethy1–2,3-dihydro-lH-benzo[b][l,4]diazepin-l-yl)phenyl)methanimine motifs as antimicrobial and anti-tubercular agents
•Simple o-phenylenediamine was successfully utilized for the synthesis of a series of new substituted benzylidene-based benzodiazepines 3a-l in three steps.•Comparative study of the synthesis of 3a-l showed that microwave assisted method was better than conventional heating in term of reaction time,...
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| Published in: | Scientific African Vol. 26; p. e02458 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Elsevier B.V
01-12-2024
Elsevier |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | •Simple o-phenylenediamine was successfully utilized for the synthesis of a series of new substituted benzylidene-based benzodiazepines 3a-l in three steps.•Comparative study of the synthesis of 3a-l showed that microwave assisted method was better than conventional heating in term of reaction time, easy work-up ad higher yields.•chemical structures of 3a-l were authenticated using analytical and spectral data from uv-visible, FT-IR, 1H- and 13CNMR.•All compounds were screened in vitro for their antimicrobial activities and 3b bearing 2‑chloro substituent emerged as the best antimicrobial and anti-tubercular agents among the series.•docking studies of some 2‑chloro-benzylidene-benzodiazepine 3b gave rational explanation for its outstanding antimicrobial and anti-tubercular efficacies as inhibitor of 2WGD protein.
Benzodiazepines' chemistry and synthesis as heterocyclic compounds have recently attracted a lot of attention, due to their extensive biological diversity in drug design and potential for usage in agrochemicals. Eco-friendly and highly efficient method was herein reported for the synthesis of a new series of Schiff base of benzodiazepine derivatives 3a-l using microwave-assisted approach. Firstly, 2,2,4-trimethy1–2,3-dihydro-lH-benzo[b][l,4]diazepine (1) was synthesized by AgNO3-catalyzed reaction of o-phenylenediamine with excess of acetone. Coupling of benzodiazepine 1 with 4-chloroaniline afforded intermediate benzodiazepine 2 which was subsequently reacted with benzaldehyde derivatives via microwave irradiation technique to access twelve final targeted benzodiazepine Schiff bases, 3a-l. The chemical structures of the scaffolds 3a-l were authenticated using analytical and spectroscopic data. Benzodiazepine Schiff bases 3a-l were investigated for their in vitro antimicrobial activities using Agar diffusion technique and screened for their minimum inhibitory concentration (MIC) using microtube dilution technique. Ten pathogenic organisms comprising of seven bacterial and three fungal isolates were utilized for the screening. Ciprofloxacin was the positive control for antibacterial screening while fluconazole was engaged as the positive control for the antifungal screening. The most efficacious antimicrobial agent among the series was (E)-l-(2-Chloropheny1)-N-(4-(2,2,4-trimethyl-2,3-dihydro-lH-benzo[b][l,4] diazepinlyl)phenyl)methanimi ne (3b) with a MIC value of 3.13 µg/mL and MBC of 6.25 µg/mL among all the synthesized compounds synthesized and screening for antimicrobial assessment. Compound 3b also emerged as the best anti-tubercular agent IC50 of 40 µg/mL against Mycobacterium tuberculosis, Mycobacterium bovis and H37Rv
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| ISSN: | 2468-2276 2468-2276 |
| DOI: | 10.1016/j.sciaf.2024.e02458 |