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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

Design, Synthesis, Docking, Characterization and Biological Screening of Novel Azetidinone Derivatives of Nicotinic Acid

Author(s): Amuthalakshmi Sivaperuman, Ramalakshmi Natarajan*, Arunkumar Subramani and Prabakaran Angamuthu

Volume 18, Issue 3, 2022

Published on: 30 November, 2021

Article ID: e021221196725 Pages: 11

DOI: 10.2174/1573407217666210922120323

Price: $65

Abstract

Background: The prevailing multiple drug resistance among the bacterial species is alarmingly rising day to day, becoming a global threat. Many infectious diseases have become untreated due to the development of resistance in bacterial species, which have a considerable impact on mortality.

Methods: In this present study, we aimed to synthesize a series of 12 compounds [S1-S12], which are azetidinone derivatives of nicotinic acid. The in vitro antibacterial studies were performed against certain species of gram-negative and gram-positive bacteria. Molecular docking studies were performed to identify the affinity towards the target protein. The antioxidant study was also performed for the synthesized compounds.

Results: All the synthesized compounds exhibited moderate to potent antibacterial activity with a MIC range of 9.8-21.6 μgmL-1, compounds were active against all tested micro-organisms. The compounds substituted with electron-donating groups like hydroxyl showed higher antioxidant activity compared to others. Docking studies were performed on the active site of DNA gyrase [PDBID: 5L3J,2XCT, 1W7Q].

Conclusion: The present study reveals that the compounds synthesized exhibit very good antimicrobial activity and antioxidant activity. Therefore, these compounds may be used as a lead for the anticancer, anti-tubercular and other chemotherapeutic agents in future studies.

Keywords: Multiple drug resistance, azetidinone derivatives, MIC results, docking, biological screening, nicotinic acid.

Graphical Abstract

[1]
Nikaido, H. Multidrug resistance in bacteria. Annu. Rev. Biochem., 2009, 78, 119-146.
[http://dx.doi.org/10.1146/annurev.biochem.78.082907.145923] [PMID: 19231985]
[2]
Rouveix, B. Clinical implications of multiple drug resistance efflux pumps of pathogenic bacteria. J. Antimicrob. Chemother., 2007, 59(6), 1208-1209.
[http://dx.doi.org/10.1093/jac/dkl564] [PMID: 17507420]
[3]
Tenover, F.C. Mechanisms of antimicrobial resistance in bacteria. Am. J. Med., 2006, 119(6)(Suppl. 1), S3-S10.
[http://dx.doi.org/10.1016/j.amjmed.2006.03.011] [PMID: 16735149]
[4]
El-Sayed, R. Synthesis, antibacterial and surface activity of 1, 2, 4-triazole derivatives. Grasas Aceites, 2006, 57(2), 180-188.
[http://dx.doi.org/10.3989/gya.2006.v57.i2.35]
[5]
Mogilaiah, K.; Sveenivasulu, B.; Rao, R.G. Synthesis and antimicrobial activity of 1, 3, 4-oxadiazolyl-1, 8-naphtho pyridines. Indian J. Chem., 1996, 35, 339-344.
[6]
Laddi, U.V.; Desai, S.R.; Somannavar, Y.S.; Bennur, R.S.; Bennur, S.C. Some new 3-substituted-4-amino-5-mercapto-4 (H)-1, 2, 4-triazoles as nonsteroidal antiinflammatory agents. Ind. J. Chem. Section B, 1998, 37, 461-467.
[http://dx.doi.org/10.1002/chin.199839131]
[7]
Ilkay, K.; Estra, T.; S., Gu, Küçükgüzel, S.G.; Rollas, S.; Clercq, E.D. Synthesis of some novel thiourea derivatives obtained from 5-[(4-aminophenoxy)methyl]-4-alkyl/aryl-2,4-dihydro-3H-1,2,4- triazole-3-thiones and evaluation as antiviral/anti-HIV and anti-tuberculosis agents. Eur. J. Med. Chem., 2007, 43(2), 381-392.
[8]
Patel, N.B.; Khan, I.H. Synthesis of 1,2,4-triazole derivatives containing benzothiazoles as pharmacologically active molecule. J. Enzyme Inhib. Med. Chem., 2011, 26(4), 527-534.
[http://dx.doi.org/10.3109/14756366.2010.535794] [PMID: 21714763]
[9]
Witkowski, J.T.; Robins, R.K.; Khare, G.P.; Sidwell, R.W. Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides. J. Med. Chem., 1973, 16(8), 935-937.
[http://dx.doi.org/10.1021/jm00266a014] [PMID: 4355593]
[10]
Jo, Y.W.; Im, W.B.; Rhee, J.K.; Shim, M.J.; Kim, W.B.; Choi, E.C. Synthesis and antibacterial activity of oxazolidinones containing pyridine substituted with heteroaromatic ring. Bioorg. Med. Chem., 2004, 12(22), 5909-5915.
[http://dx.doi.org/10.1016/j.bmc.2004.08.025] [PMID: 15498667]
[11]
El-Sayed, W.A.; Khalaf, H.S.; Mohamed, S.F.; Hussien, H.A.; Kutkat, O.M.; Amr, A.E. Russ. J. Gen. Chem., 2007, 87(10), 2444-2453.
[http://dx.doi.org/10.1134/S1070363217100279]
[12]
Al-Omar, M.A.; Youssef, K.M.; El-Sherbeny, M.A.; Awadalla, S.A.A.; El-Subbagh, H.I. Synthesis and in vitro antioxidant activity of some new fused pyridine analogs. Arch. Pharm. (Weinheim), 2005, 338(4), 175-180.
[http://dx.doi.org/10.1002/ardp.200400953] [PMID: 15864787]
[13]
Altaf, A.A.; Shahzad, A.; Gul, Z.; Rasool, N.; Badshah, A.; Lal, B.; Khan, E. A review on the medicinal importance of pyridine derivatives. J. Drug Design and Medicinal Chem., 2015, 1(1), 1-11.
[14]
Sajja, Y.; Vanguru, S.; Vulupala, H.R.; Bantu, R.; Yogeswari, P.; Sriram, D.; Nagarapu, L. Design, synthesis and in vitro anti-tuberculosis activity of benzo[6,7]cyclohepta[1,2-b]pyridine-1,2,3-triazole derivatives. Bioorg. Med. Chem. Lett., 2017, 27(23), 5119-5121.
[http://dx.doi.org/10.1016/j.bmcl.2017.10.071] [PMID: 29113761]
[15]
Kumar, S.; Das, S.K.; Dey, S.; Maity, P.; Guha, M.; Choubey, V.; Panda, G.; Bandyopadhyay, U. Antiplasmodial activity of [(aryl)arylsulfanylmethyl]Pyridine. Antimicrob. Agents Chemother., 2008, 52(2), 705-715.
[http://dx.doi.org/10.1128/AAC.00898-07] [PMID: 18025110]
[16]
Helal, M.H.; El-Awdan, S.A.; Salem, M.A.; Abd-elaziz, T.A.; Moahamed, Y.A.; El-Sherif, A.A.; Mohamed, G.A. Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2015, 135, 764-773.
[http://dx.doi.org/10.1016/j.saa.2014.06.145] [PMID: 25150427]
[17]
Pandey, V.K.; Gupta, V.D.; Upadhyay, M.; Upadhyay, M.; Singh, V.K.; Tandon, M. Synthesis, characterization and biological activity of 1, 3, 4-substituted 2-azetidinones. Ind. J. Chem., 2005, 44, 158-162.
[18]
Govindarajan, R.; Jamela, H.J.; Butt, A.R. Biological evaluation of some novel quinoxaline bearing azetidinones including leptospirocidal study. Ind. J. Het. Chem, 2003, 12, 183-187.
[19]
Srivastava, S.K.; Srivastava, S.; Srivastava, S.D. Synthesis of new carbazolyl-thiadiazol-2-oxo-azetidines: Antimicrobial, anticonvulsant and anti-inflammatory agents. IJCB, 1999, 38B(2), 183-187.
[20]
Shah, M.; Parikh, K.; Parekh, H. Synthesis of thiazolidinones and azetidinones from hydrazino thieno pyrimidines as potential antimicrobial agents. Indian J. Chem, 1998, 37b, 73-77.
[21]
Hogale, M.; Uthale, A. Synthesis and biological activity of 4-(N-arylidene acetylhydrazido)-1, 4-benzothiazin-2, 3-diones, azetidinones and thiazolidinones. Proceedings the Ind. Academy Sci.-Chemical Sci., 1990, 102(4), 535-540.
[22]
Parikh, K.A.; Oza, P.S.; Bhatt, S.B.; Parikh, A.R. A synthesis of some new 2-azetidinones as potential antitubercular agents. IJCB, 2000, 39B(9), 716-718.
[23]
Vashi, B.S.; Mehta, D.S.; Shah, V.H. Synthesis and biological activity of 4‐Thiazolidinones, 2‐Azetidinones, 4‐Imidazolinone derivatives having thymol moiety. Chem. Inform., 1995, 26(47), 353-359.
[24]
Xianxiu, Xu.; Renzhong, Fu. Bioorg. Med. Chem. Lett., 2007, 17, 101-104.
[http://dx.doi.org/10.1016/j.bmcl.2006.09.078] [PMID: 17049851]
[25]
Vashi, D.S.; Mehta, D.S.; Shaw, V.H. Synthesis of 2, 5-disubstituted-1,3, 4-oxadiazole, 1, 5-disubstituted-2-mercapto-1, 3, 4-triazole and 2,5-disubstituted-1, 3, 4-thiadiazole derivatives as po tential antimicrobial agents. Indian J. Chem., 1995, 34-B, 111-115.
[26]
Sridhar, S.K.; Pandeya, S.N.; Stables, J.P.; Ramesh, A. Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin derivatives. Eur. J. Pharm. Sci., 2002, 16(3), 129-132.
[http://dx.doi.org/10.1016/S0928-0987(02)00077-5] [PMID: 12128166]
[27]
Sridhar, S.K.; Pandeya, S.N.; De Clercq, E. Synthesis and anti-HIV activity of some isatin derivatives. Boll. Chim. Farm., 2001, 140(5), 302-305.
[PMID: 11680082]
[28]
Sridhar, S.K.; Ramesh, A. Synthesis and Pharmacological Activities of Hydrazones, Schiff and Mannich Bases of Isatin Derivatives. J. Ind Drugs., 2001, 38, 174.
[29]
Reynolds, J.E. Martindale: The extra pharmacopoeia; The Pharmaceutical Press: London, UK, 1982.
[30]
Hawkey, P.; Lewis, D., Eds.; Medical bacteriology: a practical approach; OUP Oxford, 2003, Vol. 265, .
[31]
Spanou, C.; Manta, S.; Komiotis, D.; Dervishi, A.; Kouretas, D. Antioxidant activity of a series of Fluorinated pyrano-nucleoside analogues of N4-benzoyl cytosine andN6-benzoyl adenine. Int. J. Mol. Sci., 2007, 8(7), 695-704.
[http://dx.doi.org/10.3390/i8070695]
[32]
Rajeshwar, Y.; Kumar, G.S.; Gupta, M.; Mazumder, U.K. Studies on in vitro antioxidant activities of methanol extract of Mucuna pruriens (Fabaceae) seeds. Eur Bull Drug Res, 2005, 13(1), 31-39.
[33]
Ananthanarayan, R.; Panicker, J.C.K. Textbook of microbiology: Orient Longman Ltd; 5th ed. , 1987.

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