Research Journal of Pharmacy and Technology

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Synthesis, Antimicrobial Evaluation and Docking Studies of Novel 4- Acetamido-3-Aminobenzoic Acid Derivatives As Microbial Neuraminidase Inhibitors


Affiliations
1 Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur - 495009, Chhattisgarh, India
     

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Background: Neuraminidase has been considered as vital target for neuraminidase inhibitors (NAI) and designing drug against influenza like new virus strains. The objectives of research work is to synthesized novel 4-acetamido-3-(benzylideneamino)benzoic acid derivatives against microbial neuraminidase (NA) enzyme. Methods: The series of Imine/Schiff base compound were synthesized by reaction of various aldehydes with 4- acetamido-3-amino benzoic acid. Compounds were characterized by IR, 1H NMR and, 13C NMR. Evaluation of synthesized compounds was done against neuraminidase contained bacterial as well as fungal strains. Results: The Compounds 5k-5q, 5x and 5y of novel 4-acetamido-3-aminobenzoic acid derivatives were characterized as potent inhibitory action against the NA contained microbes. The zone of inhibition of these compounds at 125 μg/ml was found (16 ± 2.5), which is more than the standard compounds. Molecular docking of synthesized compounds 5k to 5q showed the highest docking score (> -9 Kj/mol). Conclusion: The compounds 5k-5q, 5x and 5y of novel 4-acetamido-3-aminobenzoic acid derivatives displayed potential neuraminidase inhibition against NA containing microbes. The molecular docking studies predict their binding mode interaction of NA inhibitor. These studies may be further employed, against the neuraminidase contained flu.

Keywords

Antimicrobial, Influenza, Molecular Modeling, Neuraminidase, Para-Amino Benzoic Acid, Schiff Base.
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  • Yu Y, Garg Y, Yu PA, Kim H.J, Patel A, Merlin TS, Uyeki TM. Peramivir use for treatment of hospitalized patients with influenza A (H1N1) pdm09 under the emergency use authorization October 2009–June 2010. Clin. Infect Dis. 2012; 55(1): 8–15.

  • Zhang J, Wang Q, Fang, H, Xu W, Liu, Du G. Design, synthesis, inhibitory activity, and SAR studies of hydrophobic paminosalicylic acid derivatives as neuraminidase inhibitors. Bio Med Chem. 2008; 16(7): 3839–3847.

  • Jim H, Kim CU. Design of Neuraminidase Inhibitors as AntiInfluenza Virus Agents. Advances in Antiviral Drug Design. 2003; 4: 99–117.

  • Yang JL, Zeng XF, Liu HP, Yu Q, Meng X, Yan XL, et, al, Synthesis of multivalent difluorinated zanamivir analogs as potent antiviral inhibitors. Tetrahedron Letters. 2016; 57: 2579–2582.

  • Samson M, Pizzorno A, Abed Y, Boivin G. Influenza virus resistance to neuraminidase inhibitors. Antiviral Research. 2013; 98(2): 174–185.

  • Camara M, Boulnois GJ, Andrew PW, Mitchell TJ. A Neuraminidase from Streptococcus pneumoniae has the Features of a Surface Protein Infection and Immunity. 1994; 62(9): 36883695.

  • Ada GL, French EL, Lind PE. Purification and properties of neuraminidase from Vibrio cholera. J. Gen. Microbiol. 1961; 24(3): 409–425.

  • Miercio EA, Pereira J. Mejia S. The Trypanosoma cruzi Neuraminidase Contains Sequences Similar to Bacterial Neuraminidases, YWTD Repeats of the Low-Density Lipoprotein Receptor and III of Fibronectin. J. Exp Modules. Med. 1991; 174: 179-191.

  • Kim C.U, Lew, W, Williams M.A. Liu H, Zhang L, Swaminathan S, et al. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J. Am. Chem Soc. 1997; 119 (4): 681-688.

  • Camara M, Boulnois GJ, Andrew PW, Mitchell TJ. A Neuraminidase from Streptococcus pneumoniae has the Features of a Surface Protein Infection and Immunity. 1994; 62 (9): 36883695.

  • Tomoko N, Kazufumi S, Torahiko T, Kazumichi K. Tadatoshi T, Tatsuo Y. Bacterial Neuraminidase Rescues Influenza Virus Replication from Inhibition by a Neuraminidase Inhibitor. PLoS ONE. 2012; 7(9): 1-12.

  • Morphy R, Rankovic Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem, 2005; 48: 6523–6543.

  • Finley, JB, Atigadda VR, Duarte F, Zhao JJ, Brouillette WJ, Air GM, Luo M. Novel Aromatic Inhibitors of Influenza Virus Neuraminidase Make Selective Interactions with Conserved Residues and Water Molecules in the Active Site. J.Mol.Biol. 1999: 293; 1107-1119.

  • Han N, Mu Y. Looking the 150-Cavity Open: In-Silico Design and Verification of Influenza Neuraminidase Inhibitors. PLoS ONE. 2012; 8(8): 1-16.

  • Liu Y. Jing F, Xu Y, Xie Y, Shi F, Fang H, et al. Synthesis and biological activity of thiazolidine-4-carboxylic acid derivatives as novel influenza neuraminidase inhibitors. Bioorganic & Medicinal Chemistry. 2011; 19: 2342–2348.

  • Karthikeyan MS, Prasad DJ, Poojary B, Bhat KS, Holla BS, Kumari NS. Synthesis and biological activity of Schiff and Mannich bases bearing 2, 4-dichloro-5-fluorophenyl moiety. Bioorg & Med Chem. 2006; 14(22): 7482–7489.

  • Bhattacharjee S, Arrora M, Moha SJ. Synthesis, Characterization and Antimicrobial Activity of Some Schiff Bases of 2-Amino-N(o-Fluorophenylcarboxamido)-4-(p-Methoxyphenyl) Thiophenes. Asian J. Research Chem. 2012; 5(11): 1399-1404.

  • Deshpande MM., Seema IH, Deshpande VG., Kulkarni PA. Synthesis Characterization and Antimicrobial Evaluation of Some New Schiff Bases. Asian J. Research Chem. 2013; 6(2): 131134.

  • Kaura A, Sharma L, Dhar VJ. Spectral and Antimicrobial Study of Some Novel Schiff Bases and Beta-Lactam Derivatives. Research J. Pharm. and Tech. 2012; 5(1): 129-132.

  • Girija K, Seethalakshmi P, Hemalatha K, Arumugam N. Synthesis and Antimicrobial Activity of some Novel Mannich Base Substituted Pyrazolone Derivatives Synthesis and Antimicrobial Activity of some Novel Mannich Base Substituted Pyrazolone Derivatives Research J. Pharm. and Tech. 2014; 7(4): 460-462.

  • Patel RC , Patel CN, Panigrahi BB, Bhaskar VH. Synthesis and SAR Study of Some New Benzhydryl Piperazine Sulfonamide and Carboxamide as Antimicrobial Agents. Asian J. Research Chem. 2009; 2(4): 448-451.

  • Singh S, Jedrzejas MJ, Air GM, Luo M, Laver WG, Brouillette WJ. Structure-based inhibitors of influenza virus sialidase. A benzoic acid leads to novel interaction. J Med Chem. 1995; 38(17): 3217–3225.

  • Zhang J, Wang Q, Fang, H, Xu W, Liu A, Du G. Design, synthesis, inhibitory activity, and SAR studies of pyrrolidine derivatives as neuraminidase inhibitors. Bioorg. Med. Chem. 2007; 15(7): 2749–2758.

  • Muthumani P, Meera R, Pratesh, Chidambaranathan N, Devi P, Kameswari B. Synthesis and Biological Evaluation of Chloroacetyl Derivatives of Some Schiff’s Bases. Research J. Pharm. and Tech. 2009; 2(4): 824-829.

  • Lunkad AS, Kothawade SN, Jadhav DV, Chaudhari PS, Bornare SP. Synthesis and Antimicrobial Activity of Some New Chalcones Containing Benzofuran and Benzofuran Schiff Bases. Research J. Pharm. and Tech. 2014; 8(3); 276-279.

  • Sheriff IAK, Shafi S. Synthesis, Characterization and Antimicrobial Activity of Novel Schiff’s Base Complexes of some Transition Metal Ions. Asian J. Research Chem. 2011; 4(4): 636639.

  • Kamala G, Srinivasan N, Shankar K, Suresh R. Synthesis, Characterization and Antimicrobial Evaluation of N-Mannich Bases of (2- Substituted Phenyl) Benzimidazole Derivatives. Asian J. Pharm. Res. 2018; 8(2): 87-93.

  • Glide, version 5.8, Schrödinger, LLC, New York, NY, 2012.

  • Protein preparation wizard Schrödinger, LLC, New York, NY., 2012.

  • Patel, V.K. and H. Rajak, Significance of Amino Group Substitution at Combretastatin A-4 and Phenstatin Analogs. Letters in Drug Design & Discovery, 2016. 13(9): p. 943-951.

  • Yang Z, Nie Y, Yang G, Zu Y, Fu Y. Zhou Li. Synergistic effects in the designs of neuraminidase ligands: Analysis from docking and molecular dynamics studies. Journal of Theoretical Biology. 2010; 267 (3): 363–374.

  • Yang Z, Nie Y, Yang G, Zu Y, Fu Y. Zhou Li. Synergistic effects in the designs of neuraminidase ligands: Analysis from docking and molecular dynamics studies. Journal of Theoretical Biology. 2010; 267 (3): 363–374.

  • Lovell SC, Davis IW, Arendall WB, Word JM, Prisant MG, Richardson JS, et al, Structure validation by C-alpha geometry: phi, psi and C-beta deviation. Proteins: Structure Function & Genetics. 2002; 50(3): 437-450.

  • Comparison of Several Molecular Docking Programs: Pose Prediction and Virtual Screening Accuracy, Journal of Chemical Information and Modeling, 2009; 49(6):1455-74.

  • Venkatramani L, Johnson ES, Kolavi G, Air GM, Brouillette WJ, et al. Crystal structure of a new benzoic acid inhibitor of influenza neuraminidase bound with a new tilt induced by over packing subsite C6. BMC Structural Biology. 2012; 7 (12): 1-11.

  • Poonam I, Shashikant B, Bhagyashri S, Asha H, Chintamani J. Structure Optimization of Neuraminidase Inhibitors as Potential Anti- Influenza (H1N1Inhibitors) Agents Using QSAR and Molecular Docking Studies. Iranian Journal of Pharmaceutical Research. 2014: 13 (1): 49-65.

  • Pereira MEA, Mejia JS, Barria EO, Matzilevich D, Prioli RP. Synthesis and antibacterial activity of some Schiff bases derived from 4-aminobenzoic acid. Journal of the Serbian Chemical Society. 2005; 10: 1155-1162.

  • Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. Journal of Pharmaceutical Analysis, 2016; 6(2): 71–79.

  • Khan MSY, Husain A, Sharma S, Rashid M. Microbiological Evaluation of 4-substituted-imidazolidine Derivatives. Indian Journal of Pharmaceutical Sciences. 2012; l 74(1): 80-83.


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  • Synthesis, Antimicrobial Evaluation and Docking Studies of Novel 4- Acetamido-3-Aminobenzoic Acid Derivatives As Microbial Neuraminidase Inhibitors

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Authors

Mukesh Kumar Gupta
Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur - 495009, Chhattisgarh, India

Abstract


Background: Neuraminidase has been considered as vital target for neuraminidase inhibitors (NAI) and designing drug against influenza like new virus strains. The objectives of research work is to synthesized novel 4-acetamido-3-(benzylideneamino)benzoic acid derivatives against microbial neuraminidase (NA) enzyme. Methods: The series of Imine/Schiff base compound were synthesized by reaction of various aldehydes with 4- acetamido-3-amino benzoic acid. Compounds were characterized by IR, 1H NMR and, 13C NMR. Evaluation of synthesized compounds was done against neuraminidase contained bacterial as well as fungal strains. Results: The Compounds 5k-5q, 5x and 5y of novel 4-acetamido-3-aminobenzoic acid derivatives were characterized as potent inhibitory action against the NA contained microbes. The zone of inhibition of these compounds at 125 μg/ml was found (16 ± 2.5), which is more than the standard compounds. Molecular docking of synthesized compounds 5k to 5q showed the highest docking score (> -9 Kj/mol). Conclusion: The compounds 5k-5q, 5x and 5y of novel 4-acetamido-3-aminobenzoic acid derivatives displayed potential neuraminidase inhibition against NA containing microbes. The molecular docking studies predict their binding mode interaction of NA inhibitor. These studies may be further employed, against the neuraminidase contained flu.

Keywords


Antimicrobial, Influenza, Molecular Modeling, Neuraminidase, Para-Amino Benzoic Acid, Schiff Base.

References