SYNTHESIS, FREE RADICAL SCAVENGING AND DNA CLEAVAGE ACTIVITIES OF SOME NOVEL INDOLE DERIVATIVES
Keywords:Indolyl chalcones, Thiobarbituric acid, Free radical scavenging activity, DNA cleavage activity
Objective: Synthesis of a series of novel indole derivatives (6a-h) by condensation of indolyl chalcones (5a-h) with thiobarbituric acid to evaluate free radical scavenging and DNA cleavage activity.
Methods: The newly synthesized compounds were screened for free radical scavenging activity by DPPH method. The DNA cleavage activity of some indole derivatives was studied by agarose gel electrophoresis method. The structures of the synthesized compounds are assigned on the basis of elemental analysis, IR, 1HNMR, 13C NMR and mass spectral data.
Results: Among the synthesized compounds the simple indole derivative (6a) has very good scavenging activity, chloro and fluoro substituted indole derivatives (6g), (6h) have shown moderate activities and methyl derivatives (6e), (6f) have shown least activity compare with the standard. All the tested compounds in the series have exhibited promising DNA cleavage activity.
Conclusion: A series of novel indole derivatives were synthesized and evaluated for free radical scavenging and DNA cleavage activity. The compound (6g) was found most active among all the synthesized compounds.
NinomiyaI. Recent progress in the synthesis of indole alkaloids. J Nat Prod 1992;55:541-64.
Sundberg RJ. Indoles. London: Academic Press; 1996.
Gribble GW. Recent developments in indole ring synthesis-methodology and application. J Chem Soc Perkin Trans 2000;1:1045-75.
Richard J, Sunderberg RG, Luis JG, Parton RL, Scheiber S, Srinivasan PC, et al. Chloroacetamide photocyclization of indole derivatives. Synthesis, stereochemistry, and crystal structure of 3,7-methano-3-azacycloundecino[5,4-b]indole (deethylquebrachamine) derivatives. J Org Chem 1978;43:4859-65.
Faulkner DJ. Marine natural products. Nat Prod Rep 2001;18:1-49.
Lim KH, Hiraku O, Komiyama K, Koyano T, Hayashi M, Kam TS. Biologically active indole alkaloids from kopsiaarborea. J Nat Prod 2007;70(8):1302-7.
Pascale M. Synthesis and biological evaluation of diversely substituted indolin-2-ones. Eur J Med Chem 2008;43(11):2316-22.
Singh N, Bhaati SK, Kumar A. Thiazolyl/oxazolylformazanyl indoles as potent anti-inflammatory agents. Eur J Med Chem 2008;43:2323-30.
Renukadevi P, Biradar JS. Synthesis and antimicrobial activity of some 3,5-disubstitued-2-[1â€™-phenyl-5â€™-thialkyl-s-trizol-2-yl]indoles and 3,5-disubstituedâ€“2-[1â€™-substituedaminomethyl-4â€™-phenyl-5â€™(4â€™H)-thioneâ€“s-triazol-3â€™-yl]indoles. Indian J Heterocycl Chem 1999;9:107-12.
Panda SS, Chowdary PVR. Synthesis of novel indolyl-pyrimidine anti-inflammatory, antioxidant and antibacterial agent. Indian J Pharm Sci 2008;70:208-15.
Kathleen A, Merrill AG. PCT Int Appl WO 99. Chem Abstr 1999;130:276-65.
Bradfield CA, Bjeldanes LF. Structure-activity relationships of dietary indoles: a proposed mechanism of action as modifiers of xenobiotic metabolism. J Toxicol Environ Health 1987;21:311-23.
Dashwood RH, Uyetake L, Fong AT, Hendricks JD, Bailey GS. IN VIVO disposition of the natural anti-carcinogen indole-3-carbinol after poadministration to rainbow trout. Food Chem Toxicol 1989;27:385-92.
Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 1978;38:1410-3.
Santrucek M, Krepelka J. Antioxidants potential chemotherapeutic agents. Drugs Future 1988;37(3):121-8.
Santrucek M, Krepelka J. Antioxidants potential chemotherapeutic agents. Drugs Future 1988;37(3):973-96.
Badiget J, Manjulatha K, Girish M, Sharif A, Purohit MG. Synthesis and biological evaluation of some N-substituted indoles. Arkivok 2009;12;217-34.
Jarrahpour A, Khalili D, Clercq ED, Salmi C, Brunel JM. Synthesis, antibacterial, antifungal and antiviral activity evaluation of some new bis-schiff bases of isatin and their derivatives. Molecules 2007;12:1720-30.
Zhang WJ, Li YT, Wu ZY, Liu ZQ, Zheng ZC. Synthesis, crystal structure and DNA-binding study of a new copper (II) complex containing mixed-ligand of iminodiacetate dianion and 6-nitro-1H-benzimidazole. J Chem Crystallogr 2008;38:655-8.
PitiÃ© M, Croisy A, Carrez D, Boldron C, Meunier B. Cytostatic activity of 1, 10-phenanthroline derivatives generated by the clip-phen stratergy. Chembiochem 2006;6(4):686-91.
Maheswari PU, Roy S, Dulk HD, Barends S, Wezel GV. The square-planar cytotoxic [CuII (pyrimol) Cl] complex acts as an efficient DNA cleaver without reductant. J Am Chem Soc 2006;128(3):710-11.
Konishi M, Ohkuma H, Matsumoto K, Tsuno T, Kamei H, Miyaki T, et al. A novel antibiotic with the anthraquinone and 1,5-diyne-3-ene subunit. J Antibiot 1989;42:1449-55.
Lee MD, Dunne TS, Chang CC, Ellestad GA, Siegel MM, Morton GO, et al. Calichemicines, a novel family of antitumor antibiotics. 1. Chemistry and partial structure of calichemicine gamma. 1. J Am Chem Soc 1987;109:3464-6.
Edo K, Mizugaki M, Koide Y, Seto H, Furihata K, Otake N, et al. The structure of neocarzinostatin chromophore possessing a novel bicycle-[7,3,0]dodecadiyne system. Tetrahedron Lett 1985;26:331.
Biradar JS, Sasidhar BS, Parveen R. Synthesis, antioxidant and DNA cleavage activity of novel indole derivatives. Eur J Med Chem 2010;40:4074-8.
Tanabe Seiyaku Co Ltd Jap Pat. Novel benzothiazepine derivatives, processes for preparing the same and pharmaceutical compositions. Chem Abstr 1984;101:55532.
Whittle BA, Young EHP. The synthesis and pharmacological activity of some chloro-Î±-alkyltryptamines1. J Med Chem 1963;6(4):378â€“80.
Pathak VN, Joshi R, Gupta N. Synthesis, spectral studies and antimicrobial activities of [N-(un)alkylated-2-arylindol-3-yl] thicarbamides. Phosphorus Sulfur Silicon Relat Elem 2004;179: 2365-78.
Pathak VN, Gupta R, Garg M, Rao VM. Acid catalysed synthesis of some bis (2,2â€™-aryl-3,3â€™-alkylidine/ arylidene/ heteroaryllidene) indole and their bioactivities. Indian J Heterocycl Chem 2001;11:107-11.
Joshi KC, Pathak VN, Chand P. Synthesis of some fluorine containing indole and related compounds. J Prakt Chem 1978;320(4):701-4.
Pathak VN, Jain M, Tiwari A, Rupadevi S. New routes for synthesis of 5-Nitro-2-aryl-1H-indole-3-carboxyaldehyde and evaluation of their antimicrobial activities. Int J Pure Appl Chem 2007;2(2):245-53.
Kumara D, Kumara NM, Akamatsub K, Kusakab E, Haradac H, Itob T. Synthesis and biological evaluation of indolyl chalcones as antitumor agents. Bioorg Med Chem Lett 2010;20(13):3916-9.
Sambrook J, Fritsch EF, Maniatis EF. Molecular cloning: A laboratory manual second edition. Cold spring harbor, New York: Cold Spring Harbor Laboratory Press; 1989.
Gastpar R, Goldbrunner M, Marko D, Angerer EV. Methoxy-substituted 3-Formyl-2-phenylindoles inhibit tubulin polymerization. J Med Chem 1998;41:4965-72.
Pathak VN, Gupta R, Garg M. Synthesis, spectral, and antimicrobial studies of 1-butyl-3-substituted-4-(3-azetidinones). Heteroatm Chem 2004;15(7):494.
Biradar JS. Improved synthesis of some pyrazolines under microwave. Indian J Heterocyclic Chem 2008;18(2):141-4.
Dandia A, Sehagl V, Singh P. Synthesis of fluorineâ€“containing 2-aryl-3-pyrazolyl/puranyl/isoxazolinyl-indole derivatives as antifungal and antibacterial agents. Indian J Chem 1993;32(B):1288-91.
Pathak VN, Gupta R, Gupta N, Rao VN. Solvent-free synthesis of 3-aryl-1-(2-aryl-1H-indol-3-yl)prop-2-en-1-one and investigation of their antimicrobial activities. Int J Pure Appl Chem 2006;1(3):447-54.
Chavan RS, More HN, Bhosale AV. Synthesis and evaluation of analgesic and anti-inflammatory activity of a novel series of 3-(4,5-dihydropyrazolyl)-indoles. Int J Pharm Biomed Res 2010;1(4):135-43.