SYNTHESIS, IN VITRO ANTIBACTERIAL, TOXICITY AND MOLECULAR DOCKING ANTICANCER ACTIVITY OF NOVEL N-[(2-CHLOROQUINOLIN-3-YL) METHYLIDENE]-2-ANILINE SCHIFF'S BASES


Pradeep P S, Shrungesh Kumar T O, Prashantha N, Mahadevan K M

Abstract


Objective: Synthesis of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) and to study their in vitro antibacterial activity and in silico study towards cancer and malarial proteins.

Methods: Various N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by using 2-chloro-3-formyl quinoline and different anilines in presence of acetic acid as catalyst. All the new compounds were characterized by 1H-NMR, [13]C-NMR and LCMS analysis. The compounds 3a-j was subjected to antibacterial activity. In silico molecular properties were predicted using various online cheminformatic tools, the binding interactions with Human DNA topoisomerase I and Plasmodium falciparum lactate dehydrogenase proteins was studied through molecular docking and Irinotecan and mefloquine were used as reference drugs.

Results: Fairly good yield of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by convenient and economical procedure. The preliminary in silico pharmacokinetics study reveals that the compounds 3a-j shows excellent drug like property. The toxicity profile of compounds 3a-h was found safe. The compounds 3a-j was exhibited promising MIC values against the both S. aureus and E. coli. Similarly the docking results predict that the compound 3d shown highest interaction by forming two hydrogen bonds against the cancer protein with the interaction energy-20.696 kcal/mol. Compound 3c exhibits highest dock score of-45.703 kcal/mol with two hydrogen bonds against malarial protein.

Conclusion: From the results of docking studies of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j), it has been concluded that the compounds were found to exhibit multifunctional lead property, hence these compounds are worth to be considered as potential lead molecules for further study.

Keywords: N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline, 2-chloro-3-formyl quinoline, antibacterial, Molecular docking, ADMET

| PDF | HTML |

References


Venkatesh P. Synthesis, characterization and antimicrobial activity of various schiff base complexes of Zn (II) and Cu (II) ions. Asian J Pharm Health Sci 2011;1:8-11.

Miri R, Razzaghi-asl N, Mohammadi MK. QM study and conformational analysis of an isatin Schiff base as a potential cytotoxic agent. J Mol Model 2013;19(2):727-35.

Avaji PG, Vinod Kumar CH, Patil SA, Shivananda KN, Nagaraju C. Synthesis, spectral characterization, in-vitro microbiological evaluation and cytotoxic activities of novel macrocyclic bis hydrazine. Eur J Med Chem 2009;44(9):3552-9.

Sondhi SM, Singh N, Kumar A, Lozach O, Meijer L. Synthesis, anti-inflammatory, analgesic and kinase (CDK-1, CDK-5 and GSK-3) inhibition activity evaluation of benzimidazole/benzoxazole derivatives and some Schiff’s bases. Bioorg Med Chem 2006;14(11):3758-65.

Ershad S, Sagathforoush L, Karim-Nezhad G, Kangari S. Electrochemical behavior of N2SO Schiff-base Co (II) complexes in non-aqueous media at the surface of solid electrodes. Int J Electrochem Sci 2009;4(6):846-54.

Li S, Chen S, Lei S, Ma H, Yu R, Liu D. Investigation on some Schiff bases as HCl corrosion inhibitors for copper. Corros Sci 1999;41(7):1273-87.

Dhar DN, Taploo CL. Schiff bases and their applications. J Sci Ind Res 1982;41(8):501-6.

Tisato F, Refosco F, Bandoli G. Structural survey of technetium complexes. Coord Chem Rev 1994;135(136):325-97.

Sridhar SK, Pandeya SN, Stables JP, Ramesh A. Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin derivatives. Eur J Pharm Sci 2002;16:129-32.

Ashraf M, Wajid A, Mahmood K, Maah M, Yusoff I. Spectral Investigation of the activities of amino substituted bases. Orient J Chem 2011;27(2):363–72.

Golcu A, Tumer M, Demirelli H, Wheatley R. Cd(II) and Cu(II) complexes of polydentate Schiff base ligands: synthesis, characterization, properties and biological activity. Inorg Chim Acta 2005;358(6):1785-97.

Pandeya SN, Sriram D, Nath G, De Clercq E. Synthesis, antibacterial, antifungal and anti-HIV activity of Schiff and Mannich bases of isatin with N-[6-chlorobenzothiazol-2-yl]thiosemicarbazide. Indian J Pharm Sci 1999;61:358-61.

Rahul Pater V, Se Won Park. Synthesis of thiophenyl schiff bases via buchwald-hartwig coupling of piperazines to quinoline motif. Curr Org Synth 2014;11(4):621-5.

Dutta B, Some S, Ray JK. Thermal cyclization of 3-arylamino-3-(2-nitrophenyl)-propenal Schiff base hydrochlorides followed by triethyl phosphite mediated deoxygenation: a facile synthesis of quindolines. Tetrahedron Lett 2006;47(3):377-9.

Filler R. In: Banks RE. edotirs. Organofluorine chemicals and their industrial applications. London: Ellis Horwood; 1979.

Inouye Y, Tezuka K, Takeda W, Sugai S. Synthetic utilization of methyl 2-(F-methyl)-2-hydryl-F-propyl ether. Part III [1]. A simple one-pot preparation and derivatization of 2-alkylthio-5-(F-methyl)-6-fluoro-3,4-dihydro-4(3H)-pyrimidinones. J Fluorine Chem 1987;35(2):275-85.

Cunico W, Cechinel CA, Bonacorso HG, Martins MAP, Zanatta N, De Souza MVN, et. al. Antimalarial activity of 4-(5-trifluoro methyl-1H-pyrazol-1-yl)-chloroquine analogues. Bioorg Med Chem Lett 2006;16(3):649-53.

Rathelot P, Vanelle P, Gasquet M, Delmas F, Crozet MP, Maldonado J, et al. Synthesis of novel functionalized 5-nitroisoquinolines and evaluation of in vitro antimalarial activity. Eur J Med Chem 1995;6:503-8.

Jesmin M, Ali MM, Khanam JA. Antitumour activities of some Schiff bases derived from benzoin, salicylaldehyde, amino phenol and 2,4 dinitrophenyl hydrazine. Thai J Pharm Sci 2010;34:20-31.

Akranth M, OmPrakash T, Rikta S, Mohammad RA, Sandeep S, Akhter M, et al. Quinoline: a versatile heterocyclic. Saudi Pharm J 2013;21:1-12.

Kiran Kumar HC, Mahadevan KM, Manjappa KB. High throughput one pot synthesis of 2-methylquinolines. Tetrahedron Lett 2013;54:1368-70.

Bindu PJ, Mahadevan KM, Ravikumar Naik TR. An efficient one pot synthesis and photo-induced DNA cleavage studies of 2-chloro-3-(5-aryl-4,5-dihydroisoxazol-3-yl)quinolines. Bioorg Med Chem Lett 2012;22(19):6095-8.

Bindu PJ, Mahadevan KM, Ravikumar Naik TR. Sm(III)nitrate-catalyzed one-pot synthesis of furano[3,2c]-1,2,3,4-tetrahydroquinolines and DNA photocleavage studies. J Mol Struct 2012;1020:142-7.

Kirankumar HC, Mahadevan KM, Prabhakara VP, Srinivasa A. One pot Synthesis of medicinally important cis-2-Methyl-4-amino substituted-1,2,3,4-tetrahydroquinoline. Chin J Chem 2012;30:534-40.

Bindu PJ, Mahadevan KM, Satyanarayan ND, RavikumarNaik TR. Synthesis and DNA cleavage studies of novel quinoline oxime esters. Bioorg Med Chem Lett 2012:22:898-900.

Prabhakara VP, Sherigara BS, Mahadevan KM, Vijaykumar H. Synthesis and DNA cleavage studies of novel quinoline oxime esters. Synth Commun 2010;40:2220-31.

Srinivasa A, Mahadevan KM, Vijaykumar H. Imino diels-alder reactions: efficient synthesis of 2-Aryl-4-(2’-oxopyrrolidinyl-1’)-1,2,3,4-tetrahydroquinolines catalyzed by antimony (III) Sulphate. Monatsh Chem 2008:139:255-9.

Siddalingamurthy E, Mahadevan KM, Jagadeesh NM, Kumara MN. Synthesis and docking study of 3-(N-alkyl/aryl piperidyl) indoles with serotonin-5HT, H1 and CCR2 receptors antagonist. Int J Pharm Pharm Sci 2014;6:475-82.

Jagadeesh NM, Mahadevan KM, Kumara MN, Prashantha N. Synthesis and molecular docking study of N-alkyl/aryl-2-aryl indol-3-yl glyoxylamides as novel anticancer agents. Int J Pharm Pharm Sci 2014;6:921-6.

Jagadeesh NM, Mahadevan KM, Preenon B. Synthesis, molecular docking and fluorescent properties of novel (E)-3-(9-ethyl-9H-carbazol-3yl)-1-phenylprop-2-en-1-ones. Int J Pharm Pharm Sci 2014;6(10):317-25.

Siddalingamurthy E, Mahadevan KM, Jagadeesh NM, Kumara MN. Synthesis of novel γ-carboline derivatives and there in silico studies on 5HT1, H1 and CCR2 antagonist receptors. Int J Pharm Pharm Sci 2014;6(10):548-54.

Shrungesh Kumar TO, Mahadevan KM, Kumara MN. Synthesis and cytotoxic studies of 2,3-dimethylindoles and tetrahydrocarbazoles. Int J Pharm Pharm Sci 2014;6(2):137-40.

Tepe B, Donmez E, Unlu M, Candan F, Daferera D, Vardar-Unlu, et al. Antimicrobial and antioxidative activities of the essential oils and methanol extracts of Salvia cryptantha (Montbret et Aucher ex Benth.) and salvia multicaulis (Vahl). Food Chem 2004;84(4):519-25.

Hou TJ, Xu XJ. Recent development and application of virtual screening in drug discovery: an overview. Curr Pharm Des 2004;10:1011-33.

Lipinski CA, Lombardo L, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 2001;46:3-26.

Zhao YH, Abraham MH, Lee J, Hersey A, Luscombe CN, Beck G, et al. Rate-limited steps of human oral absorption and QSAR studies. Pharm Res 2002;19:1446-57.

Desai NC, Kotadiya GM, Trivedi AR. Studies on molecular properties prediction, antitubercular and antimicrobial activities of novel quinoline based pyrimidine motifs. Bioorg Med Chem Lett 2014;24:3126-30.

Actelion’s property explorer, Thomas Sander, Actelion’s Pharmaceuticals Ltd, Gewerbestrasse 16, Allschwil, Switzerland; 2001. p. 4123.

Proudfoot JR. Drugs, leads, and drug-likeness: an analysis of some recently launched drugs. Bioorg Med Chem Lett 2002;12(12):1647-50.

Discovery Studio, version 2.1: Accelrys, Inc: San Diego, CA, USA; 2012.

Prija P, Shikhar G, Madhu C, Rashmi T, Anil SB, Garima G, et al. 2D-QSAR, Docking studies and In Silico ADMET prediction of polyphenolic acetates as substrates for protein acetyltransferase function of glutamine synthetase of mycobacterium tuberculosis. ISRN Struct Biol 2013;12:1-12.

Discovery Studio, version 3.5: Accelrys, Inc: San Diego, CA, USA; 2012.

Laskowski RA, Rullmannn JA, MacArthur MW, Kaptein R, Thornton JM. AQUA and Procheck-NMR: programs for checking the quality of protein structures solved by NMR. J Biomol NMR 1996;8(4):477-86.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. 2000. The protein data bank. Nucleic Acids Res 2000;28:235-42.

Wu G, Robertson DH, Brooks CL, Vieth M. Detailed analysis of grid-based molecular docking: A case study of Cdocker—A CHARMm-based MD docking algorithm. J Comput Chem 2003;24:1549-62.

Venkatachalam CM, Jiang X, Oldfield T, Waldman M. Ligand fit: a novel method for the shape-directed rapid docking of ligands to protein active sites. J Mol Graph Model 2003;21:289-307.

Chohan ZH, Youssoufi MH, Jarranpour A, Hadda TB. Identification of antibacterial and antifungal pharmacophore sites for potent bacteria and fungi inhibition: indolenyl sulfonamide derivatives. Eur J Med Chem 2010;45:1189-99.

Romero BAR, Kouznetsov VV, Zacchino SA. Synthesis and in vitro evaluation of antifungal properties of some 4-Aryl-3-Methyl-1,2,3,4-Tetrahydroquinolines Derivatives. Univ Sci 2015;20(2):177-89.

Bevan CD, Lloyd RS. A high throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates. Anal Chem 2000;72:1781-7.

Susnow RG, Dixon SL. Use of robust classification techniques for the prediction of human Cytochrome P450 2D6 inhibition. J Chem Inf Comput Sci 2003;43:1308-15.




About this article

Title

SYNTHESIS, IN VITRO ANTIBACTERIAL, TOXICITY AND MOLECULAR DOCKING ANTICANCER ACTIVITY OF NOVEL N-[(2-CHLOROQUINOLIN-3-YL) METHYLIDENE]-2-ANILINE SCHIFF'S BASES

Date

15-07-2015

Additional Links

Manuscript Submission

Journal

International Journal of Current Pharmaceutical Research
Vol 7, Issue 3, 2015 Page: 37-46

Online ISSN

0975-7066

Statistics

323 Views | 148 Downloads

Authors & Affiliations

Pradeep P S
Department of Post Graduate Studies and Research in Chemistry, School of Chemical Sciences, Kuvempu University, P. G. Centre, Kadur, Karnataka 577548, India

Shrungesh Kumar T O
Department of Post Graduate Studies and Research in Chemistry, School of Chemical Sciences, Kuvempu University, P. G. Centre, Kadur, Karnataka 577548, India

Prashantha N
Department of Medicinal Chemistry, Scientific Bio-Minds, Bangalore 560092, Karnataka, India

Mahadevan K M
Department of Post Graduate Studies and Research in Chemistry, School of Chemical Sciences, Kuvempu University, P. G. Centre, Kadur, Karnataka 577548, India,


Refbacks

  • There are currently no refbacks.