Drug Res (Stuttg) 2019; 69(05): 271-276
DOI: 10.1055/a-0672-0804
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Biological Evaluation of Novel 5-Oxo-1-Phenylpyrrolidine-3-Carboxylic Acid Analogs

Poornima Devi
1   Department of Chemistry, University of Lucknow, Lucknow, India
,
Abha Bishnoi
1   Department of Chemistry, University of Lucknow, Lucknow, India
,
Krishna Srivastava
2   Department of Chemistry, Shri Ramswaroop Memorial University, Barabanki, India
,
Sunil Kumar
3   Institute of Bio-Sciences & Technology, Shri Ramswaroop Memorial University, Barabanki, India
,
Ankita Srivastava
3   Institute of Bio-Sciences & Technology, Shri Ramswaroop Memorial University, Barabanki, India
,
Shaheen Fatma
2   Department of Chemistry, Shri Ramswaroop Memorial University, Barabanki, India
› Author Affiliations
Further Information

Publication History

received 04 June 2018

accepted 04 August 2018

Publication Date:
07 September 2018 (online)

Abstract

A number of 5-oxo-1-phenyl-4-(substituted methyl) pyrrolidine-3-carboxylic acid derivatives bearing pyrrolidine ring and methylamino residues in their structure were synthesized as potential antibacterial drugs. The chemical structures of all the compounds were established by their UV-Vis absorption spectroscopy, IR, 1H, 13C NMR and mass spectroscopy. The in vitro antibacterial screening of all novel compounds was done against gram-positive Staphylococcus aureus, Bacillus subtilis and gram-negative Pseudomonas aeruginosa. The results revealed that compounds 5d, e, f and g showed moderate to good activity against the tested microbes.

Supporting Information

 
  • References

  • 1 Jackson SK, Karadeolian A, Driega AB. et al. Stereodivergent methodology for the synthesis of complex pyrrolidines. J Am Chem Soc 2008; 130 12 4197
  • 2 Mayol-Llinàs J, Nelson A, Farnaby W. et al. Assessing molecular scaffolds for CNS drug discovery. Drug Discov Today 2017; 22: 965-969
  • 3 (a) Dandia A, Khan S, Soni P. et al. Diversity-oriented sustainable synthesis of antimicrobial spiropyrrolidine/thiapyrrolizidine oxindole derivatives: New ligands for a metallo-β-lactamase from Klebsiella. Bioorg Med Chem Lett 2017; 27: 2873-2880 (b) Zong X, Cai J, Chen J, et al. Design and synthesis of imidazole N–H substituted amide prodrugs as inhibitors of hepatitis C virus replication. Bioorg Med Chem Lett 2015; 25:3147–3150
  • 4 Just-Baringo X, Albericio F, Álvarez M. Thiopeptide Antibiotics: Retrospective and Recent Advances. Mar Drugs 2014; 12: 317-351
  • 5 (a) Ersen D, Ülger M, Mangelinckx S. et al. Synthesis and anti(myco)bacterial activity of novel 5,5-diphenylpyrrolidine N-aroyl thiourea derivatives and a functionalized hexahydro-1H-pyrrolo[1,2-c]imidazole. Med Chem Res 2017; 26: 2152-2160 . (b) Gemili M, Sari H, Ulger M, Sahin E, Nural Y Pt(II) and Ni(II) complexes of octahydropyrrolo[3,4-c]pyrrole N-benzoylthiourea derivatives: Synthesis, characterization, physical parameters and biological activity, Inorg Chim Acta 2017; 463:88–96
  • 6 (a) Weng Z, Shao X, Graf D. et al. Identification of fused bicyclic derivatives of pyrrolidine and imidazolidinone as dengue virus-2 NS2B-NS3 protease inhibitors. Eur J Med Chem 2017; 125: 751-759 (b) Kang I-J, Hsu S-J, Yang H-Y, et al. A Potent, Selective, and Orally Bio available HCV NS5A Inhibitor for Treatment of Hepatitis C Virus: (S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl)pyrrolidine-2-carboxamide. J Med Chem 2017;60:228–247
  • 7 Obniska J, Rapacz A, Rybka S. et al. Synthesis, and anticonvulsant activity of new amides derived from 3-methyl-or 3-ethyl-3-methyl-2, 5-dioxo-pyrrolidin-1-yl-acetic acids. Bioorg Med Chem 2016; 24: 1598-1607
  • 8 (a) Omar HA, Zaher DM, Srinivasulu V. et al. Al-Tel TH Design, synthesis and biological evaluation of new pyrrolidine carboxamide analogues as potential chemotherapeutic agents for hepatocellular carcinoma. Eur J Med Chem 2017; 139: 804-814 (b) Aguilar A, Lu J, Liu L, et al. Discovery of 4-((3′R,4′S,5′R)-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″oxodi spiro [cyclohexane-1,2′-pyrrolidine-3′,3″-indoline] 5′carboxamido) bicycle [2.2.2] octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development. J Med Chem 2017; 60:2819–2839. (c) Lotfy G, Said MM, El Sayed H, et al. .Synthesis of new spirooxindole-pyrrolothiazole derivatives: Anti-cancer activity and molecular docking. Bioorg Med Chem 2017; 25:1514–1523
  • 9 Almajan GL, Barbuceanu SF, Almajan ER. et al. Synthesis, characterization and antibacterial activity of some triazole Mannich bases carrying diphenylsulfone moieties. Eur J Med Chem 2009; 44: 3083-3089
  • 10 Ashok M, Holla BS, Poojary B. Convenient one pot synthesis and antimicrobial evaluation of some new Mannich bases carrying 4-methylthiobenzyl moiety. Eur J Med Chem 2007; 42: 1095-1101
  • 11 Mahajan R, Sharma RL. Synthesis of various novel heterocyclic N-Mannich bases from variety of dihydropyrimidones and octahydropyrimidopyrimidones. Indian Journal of Chemistry 2017; 56B: 872-879
  • 12 Jose G, Tholappanavara H, Kumara S. et al. Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases. Eur J Med Chem 2017; 131: 275-288
  • 13 Gopi C, Dhanaraju MD. Synthesis, spectroscopy characterization and biological activities of some novel 1-(3-(N,N-dimethylamino)-1-(5-substituted thiophene-2-yl) propylidene semicarbazone Mannich base derivatives. Beni-Suef University Journal of Basic and Applied Sciences 2018; 6: 2314-8535
  • 14 Li Y, Qiang X, Luo L. et al. Aurone Mannich base derivatives as promising multifunctional agents with acetyl cholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease. Eur J Med Chem 2016; 42: 1095-1101
  • 15 Mahal K, Ahmad A, Schmitt F. et al. Improved anticancer and antiparasitic activity of new lawsone Mannich bases. Eur J Med Chem 2017; 126: 21-431
  • 16 Mistry B, Patel RV, Young-Soo K. et al. Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects. Saudi Journal of Biological Sciences 2017; 24: 36-44
  • 17 Joshi S, Bilgaiyan P, Pathak A. Synthesis, spectroscopic characterization and antibacterial screening of novel Mannich bases of Ganciclovir. Arabian Journal of Chemistry 2017; 10: S1180-S1187
  • 18 Afaf H. El-masry Fahmy HH. et al. Synthesis and Antimicrobial Activity of Some New Benzimidazole Derivatives. Molecules 2000; 5: 1429-1438
  • 19 Sridhara SK, Surendra N. Pandeyab et al. A nticonvulsant activity of hydrazones. Schiff and Mannich bases of isatin derivatives Eur J of Pharma Sci 2002; 16: 129-132
  • 20 Wang B-L, Liu X-H, Zhang X-L. et al. Synthesis, Structure and Biological Activity of Novel 1,2,4-Triazole Mannich Bases Containing a Substituted Benzylpiperazine Moiety. Chem Biol Drug Des 2011; 78: 42-49
  • 21 Ahmad A, Mahal K, Padhye S. et al. Bernhard, New ferrocene modified lawsone Mannich bases with anti-proliferative activity against tumor cells. Journal of Saudi Chemical Society 2017; 21: 105-110
  • 22 Nguyen V-S, Shi L, Wang S-C. et al Synthesis of icaritin and β-anhydroicaritin mannich base derivatives and their cytotoxic activities on three human cancer cell lines. Anti-Cancer Agents in Medicinal Chemistry 2017; 17: 137-142
  • 23 Paytash LP, Sparrow E, Gathe CJ. The reaction of itaconic acid with primary amines. J Am Chem Soc 1950; 72: 1415-1416
  • 24 Bauer AW, Kirby WMM, Sherris JC. et al. Antibiotics susceptibility testing by a standard single disk method. This Week’s Citation Classics 1985; 45: 493-496
  • 25 Bauer AW, Kirby WMM, Sherris JC. et al. Antibiotic susceptibility testing by a standardized single disk method. American Journal of Clinical Pathology 1966; 45: 493-496
  • 26 Michel Gaydos J, Harrington BJ. Agar Disk Diffusion for the Quality Control Testing of Autobac Elution Disks Antimicrobial Agent and Chemotherapy. 1982; 21: 516-518
  • 27 Devi P, Fatma S, Bishnoi A. et al. Synthesis, spectroscopic and DFT studies of novel 4-(morpholinomethyl)-5-oxo-1-phenylpyrrolidine-3-carboxylic acid. Journal of Molecular Structure 2018; 1157: 551-559