Synthesis , Quantum mechanical calculation and in silico screening of novel hydrazone derivatives as Mycobacterium tuberculosis enoyl reductase inhibitors
DOI:
https://doi.org/10.7439/ijpc.v5i10.2599Abstract
A series of novel benzo hydrazide derivatives were synthesized and benzoylated. The compounds were purified and characterized by IR, NMR, Mass spectral studies. Drug likeliness assessment conferred all compounds obeying rule of thumb. Binding energy calculation revealed compounds having electron donating groups having high HOMO values (BS9, BS10, SB9, SB10). Structure based drug design was performed for 48 structures having various heterocyclic moieties, INH, and 10 compounds which are reported in literature as active Inh A inhibitors. Docking and scoring study unravels that our compounds were having 1-5 H-bonding interactions with Tyr158, Ile95, Ile194, Pro 193 H2O 856, 502, 563, and 552. Hydrophobic interactions of compounds were found to be with Ala157, Gly96, Ile215, Leu218, Met103, Tyr158, Phe97, Pro156, Ser123 and Iys165. All the compounds have good docking score compared to INH. In vitro anti oxidant activity by nitric oxide scavenging assay was also performed and the results inferred compounds having good docking score are having good activity. The compounds having electron donating groups are having good activity.Downloads
References
John S. Blanchard. Molecular mechanisms of Drug resistance in Mycobacterium Tuberculosis, Annu. Rev. Biochem., 1996; 65: 215-239.
Sunduru N, Sharma M, Chauhan P.M.S. Recent advances in the design and synthesis of Heterocycles as anti-tubercular agents, Futur. Med Chem., 2010; 2(9): 1469-1500.
Reddy Y.N, Murthy S.V, Krishna D.R, Prabhakar M.C. Role of free radicals and antioxidants in tuberculosis patients, Indian J Tuberc., 2004; 51: 213-218.
Khisimuzi , Spigelman M. Novel targets for tuberculosis drug discovery, Current opinion pharmacolo., 2006; 6: 459-467.
Mohareb R.M, Fleita D.H, Sakka O.K. Novel Synthesis of Hydrazide-Hydrazone Derivatives and Their Utilization in the Synthesis of Coumarin, Pyridine, Thiazole and Thiophene Derivatives with Antitumor Activity. Molecule., 2011; 16: 16-27.
Mohareb R.M, Mohamed A.A. The Reaction of Cyanoacetylhydrazine with ?-Bromo (4-methyl) acetophenone: Synthesis of Heterocyclic Derivatives with Antitumor Activity. Molecule., 2010; 15: 3602-3617.
Savini L, Chiasserini L, Gaeta A, Pellerano C. Synthesis and Anti-tubercular Evaluation of 4-Quinolylhydrazones. Bioorg. Med. Chem., 2002; 10: 2193
Rajput A P, Rajput S S. A novel method for the synthesis of formyl pyrazoles using vilsmeier-haack reaction. Int J Pharm Pharm Sci., 2011; 3(4): 346-351
Rollas S, Kucukguzel S.G. Biological Activities of Hydrazone Derivatives, Molecules., 2007; 12: 1910-1939.Shikha G, Shilpi G, Anis M, Hemant K, Khushbu S. Green Chemical Route towards Synthesis of Novel Acid Hydrazones. Int. J. Gr. Herb.Chem., 2012; 1(2): 140-144.
Visagaperumal D, Jaya Kumar R, Vijayaraj R, Anbalagan N. Microwave induced synthesis of some new 3-substituted-1, 3-thiazolidin-4-ones for their potent anti microbial and antitubercular activities. Int. J. ChemTech. Res., 2009; 1(4): 1048-1051.
Vicini P, Geronikaki A, Incerti M, Busonera B, Poni G, Cabras C.A, Colla P.L. Synthesis and Biological Evaluation of Benzo[d]isothiazole, Benzothiazole and Thiazole Schiff Bases. Bioorg. Med. Chem., 2003; 11: 4785
Sharma R.N, Sharma K.P, Dixit S.N. Synthesis, characterization and biological activities of some new acid hydrazones. Oriental J. Chem., 2010; 26(1): 69-74.
Commeiras L, Woodcock S.C, Baldwin J.E, Adlington R.M, Cowley R, Wilkinso P.J. New access to the 1H-pyrazolo [4, 3-c] pyridine core from bis-acetylenic-N-benzoylhydrazones. Tetrahedron., 2004; 60: 933
Narang R, Sharma S, Sriram D, Yogeeswari P, Clercq E, Pannecouque C, Balzarini J, Narasimhan B. Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of nicotinic acid benzylidene hydrazide derivatives. Med. Chem. Res., 2012; 21: 1557
Judge V, Narasimhan B, Ahuja M, Sriram D, Yogeeswari P, Clercq E.D, Pannecouque C, Balzarini J. Isonicotinic acid hydrazide derivatives: synthesis, antimicrobial activity, and QSAR studies, Med Chem Res., 2012; 21: 1451
Tripathi L, Kumar P, Singh R, Stables J P.Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides. Eur.J .Med Chem., 2012; 47: 153-166.
Nerkar A. G, Saxena A.K, .Ghone S.K, Thaker A.K. In Silico Screening, Synthesis and In Vitro Evaluation of Some Quinazolinone and Pyridine Derivatives as Dihydrofolate Reductase Inhibitors for Anticancer Activity. e-Journal of Chemistry., 2009; 6(S1): S97-102.
Nalini C.N, Arivukkarasi, Devi R. Structure based drug design, Synthesis, Characterisation and Biological evaluation of Novel Isoniazid derivatives. RASAYAN J.Chem., 2011; 4(4): 868-874.
Punkvang A, Saparpakorn P, Hannongbua S, Wolschann P, Pungpo P. Elucidating Drug-Enzyme Interactions and Their Structural Basis for Improving the Affinity and Potency of Isoniazid and Its Derivatives Based on Computer Modeling Approaches. Molecules., 2010; 15: 2791-2813.
Himaja M, Rajesh K, Venkateshwarareddy M, Asif K, Ramana M.V. Docking, Synthesis and Antitubercular evaluation of Isonicotinoyl Hydrazino-Aminoacids. Int.J.Res.Ayur.Pharm., 2011; 2(5): 1549-1552.
Yogeeswari P, Sriram D, Thirumurugan R, Raghavendran J.V, Sudhan K, Pavana R.K, Stables J. Discovery of N-(2,6-Dimethylphenyl)-Substituted Semicarbazones as Anticonvulsants: Hybrid Pharmacophore-Based Design. J. Med. Chem., 2005; 4: 6202-6211.
Kumar P.P, Rani B.L. Synthesis and characterization of new Schiff bases containing pyridine moiety and their derivatives as antioxidant agents. Int. J. ChemTech. Res., 2011; 3(1): 155-160.
Aanandhi V.M, Mansoori H.M, Shanmugapriya S, Shiny G, Shanmugasundaram P. Synthesis and In- vitro antioxidant activity of substituted Pyridinyl 1, 3, 4 oxadiazole derivatives. Res. J Phar. Biol.Chem .Sci., 2010; 1(4): 1083-1090.
Silvermann R B. The organic chemistry of drug design and action. 2nd Ed. London: Academic press (Elseveir); 2004.
Mamatha N, Murtuja S. B, Varaprasad B.F, VenkataReddy L, Abir B, Madeleine Helliwell, Mukherjee A.K, Beevi S.S, Mangamoori L.N, Mukkanti K, Sarbani P. Naproxen and ibuprofen based acyl hydrazone derivatives: Synthesis, structure analysis and cytotoxicity studies. J. Chem. pharm. Res., 2010; 2(6): 393-409.
Saleh B A, Abood H A, Miyamoto R, Bortoluzzi M. Theoretical Study of Substituent Effects on Electronic and Structural Properties of 2,4-Diamino-5-para-substituted-phenyl-6-ethyl-pyrimidines. J. Iran. Chem. Soc., 2011; 8(3): pp. 653-661.
Rando D.G, Sato D.N, Siqueira L, Malrezzi A, Leite C.Q, Amarat A.T, Ferreira E, Tavares L. C. Potential Tuberculostatic Agents. Topliss Application on Benzoic Acid [(5-Nitro-thiophen-2-yl)-methylene]-hydrazide Series. Bioorg. Med. Chem., 2002; 10: 557
Downloads
Published
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).
- The author must submit Copyright form After acceptance of the article.
How to Cite
