Aditya DIXIT, Gyanendra Kumar SHARMA, Devender PATHAK

Synthesis, antibacterial and antioxidant activity of novel 12-(N-arylmethaniminyl)indolo[1,2-c]quinazolines

The objective of the present research was to synthesize 12-(N-arylmethaniminyl)indolo[1,2-c]quinazoline derivatives (4a1-4a11) and further characterize in terms of 1H NMR, 13C NMR, FTIR and massspectrophotometry. Evaluation of their antibacterial and antioxidant activity was also carried out. Most compoundshave shown a good antioxidant activity in all the concentrations but compounds 4a7, 4a8 and 4a11 were found to bemost potent antioxidants in comparison to others with an IC50 value of 18.78 ± 1.86 μg/ml, 16.84 ± 2.60 μg/ml and 18.64± 2.40 μg/ml, respectively (DPPH method) and 18.83 ± 2.89 μg/ml, 16.61 ± 3.00 μg/ml & 16.8 ± 3.34 μg/ml, respectively(H2O2 method). Antibacterial activity was done against B. subtilis and E. coli with the help of agar well diffusion methodand it showed that all the derivatives in the series are having good antibacterial activity but compounds 4a9 and 4a11were found to be most promising antibacterial agents. It was concluded that the compounds containing substitutedanilines (4-nitro, 4-fluoro, 4-bromo and 4-chloro-2-nitro) on the methaniminyl group of 12th position ofindoloquinazoline moiety have good antioxidant and antibacterial activities.

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[1] Somei M, Yamada F. Simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Nat Prod Rep. 2003; 20: 216-242. [CrossRef]
[2] Gupta L, Talwar A, Chauhan PMS. Bis and tris indole alkaloids from marine organisms: new leads for drug discovery. Curr Med Chem. 2007; 14: 1789-1803. [CrossRef]
[3] Xu H, Lv M. Developments of indoles as anti-HIV-1 inhibitors. Curr Pharm Des. 2009; 15: 2120-2148. [CrossRef]
[4] Ran J, Huang N, Xu H, Yang Y, Lv M, Zheng YT. Anti HIV-1 agents 5: Synthesis and anti-HIV-1 activity of some Narylsulfonyl- 3-acetylindoles. Bioorg Med Chem Lett. 2010; 20: 3534-3536. [CrossRef]
[5] Ghosh AK, Gong G, Grum-Tokars V, Mulhearn DC, Baker SC, Coughlin M, Prabhakar BS, Sleeman K, Johnson ME, Mesecar AD. Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors. Bioorg Med Chem Lett. 2008; 18: 5684-5688. [CrossRef]
[6] Williams JD, Chen JJ, Drach JC, Townsend LB. Synthesis and antiviral activity of 3-formyl- and 3-Cyano-2,5,6- trichloroindole nucleoside derivatives. J Med Chem. 2004; 47: 5766-5772. [CrossRef]
[7] Andreani A, Burnelli S, Granaiola M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Varoli L, Landi L, Prata C, Berridge MV, Grasso C, Fiebig HH, Kelter G, Burger AM, Kunkel MW. Antitumor activity of bis-indole derivatives. J Med Chem. 2008; 51: 4563-4570. [CrossRef]
[8] Slater MJ, Baxter R, Bonser RW, Cockerill S, Gohil K, Parry N, Robinson E, Randall R, Yeates C, Snowden W, Walters A. Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication. Bioorg Med Chem Lett. 2001; 11: 1993-1995. [CrossRef]
[9] Mathada BSD, Mathada MBH. Synthesis and antimicrobial activity of some 5-substituted-3-phenyl-Nb-(Substituted-2- oxo-2H-pyrano [2,3-b]quinoline-3-carbonyl)-1H-indole-2-carboxyhydrazide. Chem Pharm Bull. 2009; 57: 557-560. [CrossRef]
[10] Gurkok G, Altanlar N, Suzen S. Investigation of antimicrobial activities of indole-3-aldehyde hydrazide/hydrazone derivatives. Chemotherapy. 2009; 55, 15-19. [CrossRef]
[11] Karah N, Gursoy A, Kandemirli F, Shvets N, Kaynak FB, Ozbey S, Kovalishyn V, Dimoglo A. Synthesis and structureantituberculosis activity relationship of 1H-indole-2,3-dione derivatives. Bioorg Med Chem. 2007; 15: 5888-5891. [CrossRef]
[12] Dekker WH, Selling HA, Overeem JC. Structure-activity relationships of some antifungal indoles. J Agric Food Chem. 1975; 23: 785-791. [CrossRef]
[13] Whitehead CW, Whitesitt AA. Effects of lipophilic substituents on some biological properties of indoles. J Med Chem. 1974; 17: 1298-1304. [CrossRef]
[14] Malesani G, Chiarelotto G, Dallacqua F, Vedali D. Antimicrobial properties of some 3-acyl-4,7- disubstituted indoles. Farmaco. 1975; 30: 137-146.
[15] Donawade DS, Gadaginamath GS. Some electrophilic substitution reactions on 1-substituted-3-acetyl/carbethoxy-5- hydroxy-2-methylindole and antimicrobial activity of these new indole derivatives. Indian J Chem. 2005; 44B: 1679-1685.
[16] Tsotinis A, Varvaresou A, Calogeropoulou T, Siatra-Papastaikoudi T, Tiligada A. Synthesis and antimicrobial evaluation of indole containing derivatives of 1,3,4-triazole and their open-chain counterparts. Drug Res. 1997; 47: 307-310.
[17] Varvaresou A, Tsantili-Kakoulidou A, Siatra-Papastaikoudi T, Tiligada E. Synthesis and biological evaluation of indole containing derivatives of thiosemicarbazide and their cyclic 1,2,4-triazole and 1,3,4-thiadiazole analogs. Drug Res. 2000; 50: 48-54. [CrossRef]
[18] Macchia M, Manera C, Nencetti S, Rossello A, Broccali G, Limonta D. Synthesis and antimicrobial activity of benzo[a]dihydrocarbazole and benzotetrahydrocyclohept [1,2b]indole derivatives. Farmaco. 1996; 51: 75-78.
[19] Gadaginamath GS, Kavali RR. Synthesis and antimicrobial activity of novel 4H-pyrano [2, 3-f]- indole derivatives. Indian J Chem. 1999; 38B: 178-182. [20] Bhovi MG, Gadaginamath GS. 1, 3-Dipolarcycloaddition reactions: Synthesis and antimicrobial activity of novel 1- triazolylindole and 1-triazolylbenz-[g]indole derivatives. Indian J Chem. 2005; 44B: 1068-1073.
[21] Bast A, Haenen G, Doelman C. Oxidants and antioxidants: state of the art. Am J Med. 1991; 92 (Suppl. 3C): 2-13. [CrossRef]
[22] Bulkley GB. Free radicals and other reactive oxygen metabolites: Clinical relevance and the therapeutic efficacy of antioxidant therapy. Surgery. 1993; 113: 479-483.
[23] Halliwell B, Gutteridge M. Free radicals in biology and medicine, third ed. Oxford Science Publications. Oxford University Press. 1998.
[24] Sreejayan N, Rao MN. Free radical scavenging activity of curcuminoids. Drug Res. 1996; 46: 169-171.
[25] McCord JM. Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem. 1993; 26: 351-357. [CrossRef]
[26] Cross CE, Vliet A, Neill ACO, Eiserich JP. Reactive oxygen species and the lung. Lancet. 1994; 344: 930-933. [CrossRef]
[27] Santrucek M, Krepelka J. Antioxidants from the aspect of their potential use in chemotherapy. Drugs Future. 1988; 37: 121-128. [CrossRef]
[28] Santrucek M, Krepelka J. Of particular interests are the potential protective effects of antioxidants on lipoproteins, since oxidized LDL is thought to be atherogenic. Drugs Future. 1988; 13: 973-996.
[29] Nikolic D, Breemen RB. DNA Oxidation Induced by Cyclooxygenase-2. Chem Res Toxicol. 2001; 14: 351-354. [CrossRef]
[30] Vapaatalo H. Free radicals and anti-inflammatory drugs. Med Biol. 1986; 64: 1-7.
[31] Halliwell B, Hoult JR, Blake DR. Oxidants, inflammation, and anti-inflammatory drugs. FASEB J. 1988; 2: 2867-2873. [CrossRef]
[32] Mouithys-Mickalad AML, Zheng SX, Deby-Dupont GP, Deby CM, Lamy MM, Reginster JY, Henrotin YE. In vitro study of the antioxidant properties of nonsteroidal anti-inflammatory drugs by chemiluminescence and electron spin resonance (ESR). Free Radic Res. 2000; 33: 607-621. [CrossRef]
[33] Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003; 552: 335-344. [CrossRef]
[34] Dedon PC, Tannenbaum SR. Reactive nitrogen species in the chemical biology of inflammation. Arch Biochem Biophys. 2004; 423: 12-22. [CrossRef]
[35] Billimoria AD, Cava MP. Chemistry of indolo[1, 2-c]quinazoline: An approach to the marine alkaloid Hinckdentine A. J Org Chem. 1994; 59: 6777-6782. [CrossRef]
[36] Ugur A, Mercimek B, Ozler MA, Aahin N. Antimicrobial effects of bis (2-imidazolinyl)-5,5V-dioxime and its mono- and tri-nuclear complexes. Transit Met Chem. 2000; 25: 421. [CrossRef]
[37] Malviya R, Sharma PK, Dubey SK. Antioxidant potential and emulsifying properties of kheri (Acacia chundra, Mimosaceae) gum polysaccharide. Marm Pharm J. 2017; 21(3): 701-706. [CrossRef]
[38] Ningsih IY, Zulaikhah S, Hidayat MA, Kuswandi B. Antioxidant activity of various Kenitu (Chrysophyllum cainito L.) leaves extracts from Jember. Indonesia Agric Sci Procedia. 2016; 9: 378-385. [CrossRef]