Copyright (c) 2025 D. Sherisha Bhavani, K. Madhavi, K. Swathi
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis and Antibacterial Evaluation of Novel Cyanoacrylamide Derivatives of 4-Aminosalicylic Acid
Corresponding Author(s) : D. Sherisha Bhavani
Asian Journal of Chemistry,
Vol. 37 No. 12 (2025): Vol 37 Issue 12, 2025
Abstract
In this study, novel 4-[2-cyano-3-(substituted phenyl)acrylamido]-2-hydroxybenzoic acid derivatives were synthesized starting from 4-(2-cyanoacetamido)-2-hydroxybenzoic acid. The latter was obtained through the cyanoacetylation of 4-aminosalicylic acid, leading to the formation of 4-(2-cyanoacetamido)-2-hydroxybenzoic acid as a key intermediate. The Knoevenagel condensation of the active methylene group of 4-(2-cyanoacetamido)-2-hydroxybenzoic acid was done with substituted benzaldehydes in toluene by using piperidine and glacial acetic acid as catalyzing agents. The procedure mentioned above was used to synthesize fifteen final compounds (5a-o). All the synthesized compounds were characterized by physico-chemical and spectral data. The synthesized compounds were tested for in vitro antibacterial activity by the cup-plate technique, using 0.1 mL of test solution at a concentration of 1000 µg/mL, against two Gram-positive organisms (Bacillus subtilis, Staphylococcus aureus) and two Gram-negative organisms (Escherichia coli, Proteus vulgaris). The outcomes of antibacterial activity were then compared to those obtained with the standard drug streptomycin and 4-aminosalicylic acid. Among all, the compounds 5l and 5h exhibited good antibacterial activity when compared with the standard drug.
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References
J. Lehmann, Lancet, 247, 15 (1946); https://doi.org/10.1016/S0140-6736(46)91185-3
M.N. Huffman, S.A. Thayer and E.A. Doisy, J. Biol. Chem., 133, 567 (1940); https://doi.org/10.1016/S0021-9258(18)73338-3
A.K. Chalmers and R.G. Macfarlane, Thorax, 8, 236 (1953).
WHO, Treatment of Tuberculosis: Guidelines, edn. 4 (2010).
W. Chanchaem and P. Palittapongarnpim, Tuberculosis, 82, 1 (2002); https://doi.org/10.1054/tube.2001.0314
M. Lim, J.-Y. Park, F. Abekura, H. Choi, H.-D. Kim, J. Magae, Y.-C. Chang, Y.-C. Lee and C.-H. Kim, Int. Immunopharmacol., 90, 107184 (2021); https://doi.org/10.1016/j.intimp.2020.107184
E.A. Chigorina and V.V. Dotsenko, Chem. Heterocycl. Compd., 48, 1133 (2012); https://doi.org/10.1007/s10593-012-1116-x
Z. Almarhoon, H.H. Al Rasheed and A. El-Faham, ACS Omega, 5, 30671 (2020); https://doi.org/10.1021/acsomega.0c04730
W. Zhou, H. Li, C. Xia, X. Zheng and W. Hu, Bioorg. Med. Chem. Lett., 19, 1861 (2009); https://doi.org/10.1016/j.bmcl.2009.02.081
H. Cho, M. Ueda, M. Tamaoka, M. Hamaguchi, K. Aisaka, Y. Kiso, T. Inoue, R. Ogino and T. Tatsuoka, J. Med. Chem., 34, 1503 (1991); https://doi.org/10.1021/jm00108a039
S. Son, H. Kim, H.Y. Yun, D.H. Kim, S. Ullah, S.J. Kim, Y.-J. Kim, M.-S. Kim, J.-W. Yoo, P. Chun and H.R. Moon, Bioorg. Med. Chem., 23, 7728 (2015); https://doi.org/10.1016/j.bmc.2015.11.015
F.F. Fleming, L. Yao, P.C. Ravikumar, L. Funk and B.C. Shook, J. Med. Chem., 53, 7902 (2010); https://doi.org/10.1021/jm100762r
H. Abd-El-Azim, H. Abbas, N.S. El Sayed, A.M. Fayez and M. Zewail, Int. J. Pharm., 644, 123334 (2023); https://doi.org/10.1016/j.ijpharm.2023.123334
A.M. Rabie, Curr. Res. Pharmacol. Drug Discov., 2, 100055 (2021); https://doi.org/10.1016/j.crphar.2021.100055
C. Warnke, G. Meyer zu Hörste, H.-P. Hartung, O. Stüve and B.C. Kieseier, Neuropsychiatr. Dis. Treat., 5, 333 (2009); https://doi.org/10.2147/NDT.S12160
O. Huang, W. Zhang, Q. Zhi, X. Xue, H. Liu, D. Shen, M. Geng, Z. Xie and M. Jiang, Exp. Biol. Med., 240, 426 (2015); https://doi.org/10.1177/1535370214554881
K. Madhavi and P. Sudeepthi, Int. J. Pharm. Sci. Nanotechnol., 5, 1879 (2012); https://doi.org/10.37285/ijpsn.2012.5.4.8
K. Madhavi and Ch Pavani, J. Chem. Pharm. Res., 9, 341 (2017).
K. Madhavi, K.R. Soumya and C. Subhashini, Res. J. Pharm. Biol. Chem. Sci., 8, 387 (2017).
M. Kuchana, World J. Pharm. Pharm. Sci., 3, 1800 (2014).
F.M. Sroor, K.F. Mahrous, H.I. Shafey, N.R. Eid, I.A. Abdelhamid, and N.S. Ibrahim, Med. Chem. Res., 32, 1190 (2023); https://doi.org/10.1007/s00044-023-03069-z
Y.-Y. Zhang, Q.-Q. Zhang, J.-L. Song, L. Zhang, C.-S. Jiang and H. Zhang, Molecules, 23, 1972 (2018); https://doi.org/10.3390/molecules23081972
K. Madhavi and K.V. Ramanamma, Int. J. Curr. Microbiol. Appl. Sci., 5, 364 (2016); https://doi.org/10.20546/ijcmas.2016.501.034
K. Madhavi and G. Ramya, Asian J. Pharm. Clin. Res., 10, 95 (2017); https://doi.org/10.22159/ajpcr.2017.v10i7.18290
