Volume : 12, Issue : 11, November – 2025
Title:
SYNTHESIS, ANALYSIS AND ANTI BACTERIAL ACTIVITY EVALUATION OF DI SUBSTITUTED BENZODIAZEPINE DERIVATIVES
Authors :
Marka Shalini, Dr. L. Harikiran
Abstract :
The present study focuses on the synthesis, characterization, and antibacterial evaluation of novel di-substituted benzodiazepine derivatives. Benzodiazepines, a class of heterocyclic compounds containing a fused benzene and diazepine ring, possess a wide range of biological activities, including antimicrobial, anti-inflammatory, and central nervous system effects. In this research, a series of di-substituted benzodiazepine derivatives were synthesized through a condensation reaction between o-phenylenediamine and various substituted ketones or aldehydes under controlled conditions. The synthesized compounds were purified and characterized using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), carbon-13 nuclear magnetic resonance (¹³C-NMR), and Mass Spectrometry to confirm their structures and purity.
The antibacterial potential of the synthesized derivatives was evaluated against selected Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains using the agar well diffusion method. The results indicated that several derivatives displayed moderate to significant antibacterial activity, comparable to standard antibiotics such as ciprofloxacin. The observed differences in activity suggest that the nature and position of substituents on the benzodiazepine ring significantly influence biological efficacy, indicating a clear structure–activity relationship (SAR).
Keywords: Benzodiazepine derivatives; Synthesis; Spectral analysis; Antibacterial activity; Structure–activity relationship (SAR); Heterocyclic compounds; Drug design
Cite This Article:
Please cite this article in press Marka Shalini et al., Synthesis, Analysis And Anti Bacterial Activity Evaluation Of Di Substituted Benzodiazepine Derivatives, Indo Am. J. P. Sci, 2025; 12(11).
REFERENCES:
1. Barker HA, Smyth RD, Weissbach H, Toohey JI, Ladd JN and Volcani BE. Isolation and properties of crystalline cobamide coenzymes containing Benzimidazole or 5,6- Dimethylbenzimidazole. Journal of Biological Chemistry. 1960;235(2):480- 488.
2. Patil A, Ganguly S and Surana S. A systematic review of benzimidazole derivatives as an antiulcer agent. Rasayan J Chem. 2008;1(3):447-460
3. Kubo K, Oda K, Kaneko T, Satoh H and Nohara A. Synthesis of 2-(4- Fluoroalkoxy-2-pyridyl) methyl] sulfinyl]-1H-benzimidazoles as Antiulcer Agents. Chem Pharm Bull. 1990;38(10):2853-2858.
4. Grassi A, Ippen J, Bruno M, Thomas G and Bay P. A thiazolylamino benzimidazole derivative with gastroprotective properties in the rat. Eur J Pharmacol. 1991;195(2):251-9.
5. Ozkay Y, Tunali Y, Karaca H. and Isikdag I. Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazones moiety. European Journal of Medicinal Chemistry. 2010;45(8):3293-3298.
6. Yun H, Baogen W, Yang J, Robinson D, Risen L, Ranken R, Blyn L, Eric SS. and Swayze E. 2-Piperidin-4-ylbenzimidazoles with Broad Spectrum antibacterial activities. Bioorg Med Chem Lett. 2003;13:3253-3256.
7. Metwally KA, Abdel-Aziz LM, Lashineel-SM, Husseiny MI and Badawy RH. Hydrazones of 2-aryl- -4- carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents. Bioorg Med Chem. 2006;14(24): 8675-82.
8. Spasov A, Yozhitsa L, Bugaeva I and Anisimova VA. Benzimidazole derivatives: Spectrum of pharmacological activity and toxicological properties. Pharmaceutical Chemistry Journal. 33;5:232-243.
9. Arjmand F, Mohani B and Ahmad S. Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu (II) complex. Eur J Med Chem. 2005;40(11):1103-1110.
10. Preston PN. Benzimidazoles and Congeneric Tricyclic Compounds Part 2.Wiley Interscience New York, 1980:531.
11. Abbhi V., Saini L., Mishra S., Sethi G., Kumar A. P., Piplani P. (2017). Design and Synthesis of Benzimidazole-Based Rho Kinase Inhibitors for the Treatment of Glaucoma. Bioorg. Med. Chem. 25, 6071–6085. 10.1016/J.BMC.2017.09.045
12. Abd El-All A. S., Magd-El-Din A. A., Ragab F. A., ElHefnawi M., Abdalla M. M., Galal S. A., et al. (2015). New Benzimidazoles and Their Antitumor Effects with Aurora A Kinase and KSP Inhibitory Activities. Arch. Pharm. (Weinheim) 348, 475–486. 10.1002/ardp.201400441
13. Abdel-Motaal M., Almohawes K., Tantawy M. A. (2020). Antimicrobial Evaluation and Docking Study of Some New Substituted Benzimidazole-2yl Derivatives. Bioorg. Chem. 101, 103972. 10.1016/j.bioorg.2020.103972
14. Abdelgawad M. A., Bakr R. B., Ahmad W., Al-Sanea M. M., Elshemy H. A. H. (2019). New Pyrimidine-Benzoxazole/benzimidazole Hybrids: Synthesis, Antioxidant, Cytotoxic Activity, In Vitro Cyclooxygenase and Phospholipase A2-V Inhibition. Bioorg. Chem. 92, 103218. 10.1016/j.bioorg.2019.103218
15. Abou-Seri S. M., Abouzid K., Abou El Ella D. A. (2011). Molecular Modeling Study and Synthesis of Quinazolinone-Arylpiperazine Derivatives as α1-adrenoreceptor Antagonists. Eur. J. Med. Chem. 46, 647–658. 10.1016/J.EJMECH.2010.11.045
16. Abu-Bakr S. M., Bassyouni F. A., Rehim M. A. (2012). Pharmacological Evaluation of Benzimidazole Derivatives with Potential Antiviral and Antitumor Activity. Res. Chem. Intermed. 38, 2523–2545. 10.1007/s11164-012-0569-y
17. Acar Çevik U., Kaya Çavuşoğlu B., Sağlık B. N., Osmaniye D., Levent S., Ilgın S., et al. (2020). Synthesis, Docking Studies and Biological Activity of New Benzimidazole- Triazolothiadiazine Derivatives as Aromatase Inhibitor. Molecules 25, 1642. 10.3390/molecules25071642
18. Acar Çevik U., Sağlık B. N., Korkut B., Özkay Y., Ilgın S. (2018). Antiproliferative, Cytotoxic, and Apoptotic Effects of New Benzimidazole Derivatives Bearing Hydrazone Moiety. J. Heterocyclic Chem. 55, 138–148. 10.1002/jhet.3016
19. Akhtar S., Abbas M., Naeem K., Faheem M., Nadeem H., Mehmood A. (2021). Benzimidazole Derivative Ameliorates Opioid-Mediated Tolerance During Anticancer- Induced Neuropathic Pain in Mice. Anticancer. Agents Med. Chem. 21, 365–371. 10.2174/1871520620999200818155031
20. Akhtar W., Khan M. F., Verma G., Shaquiquzzaman M., Rizvi M. A., Mehdi S. H., et al. (2017). Therapeutic Evolution of Benzimidazole Derivatives in the Last Quinquennial Period. Eur. J. Med. Chem. 126, 705–753. 10.1016/J.EJMECH.2016.12.010




