A one pot, economical, and efficient synthesis of 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2,5-diones-based derivatives 5a-l have been accomplished in single steps and in satisfactory yields from 1-(4-acetylphenyl)-pyrrole-2,5-diones 3 and phenols 4a–l. All the compounds were characterized by physical, spectroscopic, and elemental analysis. The selection of the bioassays was based on proving the drug receptor binding concept. Compounds 5g, 5k, 5h, 5i, 5a, and 5f showed the highest inhibitory antioxidant activity using ABTS methods. Compounds 5k, 5g, 5c, 5h, 5b, 5d, 5f, and 5j manifested the best protective effect against DNA damage induced by bleomycin. Moreover, an in-vitro cytotoxic activity evaluation of all synthesized compounds was against four cancer cell lines using 5-Fluorouracil as a standard anticancer drug.
Oxa-michael adducts Antioxidant Bleomycin-dependent DNA damage Lymphocyte transformation Cytotoxicity
This is a preview of subscription content, log in to check access.
The authors thank the S.V.National Institute of Technology, Surat, for the financial support, and the members of the analytical group of the Central Salt & Marine Chemicals Research Institute, Bhavnagar, and Oxygen Healthcare Private Ltd. Ahmedabad, Gujarat, India, for spectral measurements. The biological part of this work was supported by the Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. We thank Dr. Farid A Badria and his research team for excellent technical assistance.
Abdel-Wahab FB, El-Ahl AA, Badria FA (2009) Synthesis of new 2-naphthyl ethers and their protective activities against DNA damage induced by bleomycin-iron. Chem Pharm Bull 57:1348–1351CrossRefPubMedGoogle Scholar
Badawy MA, Kadry AM, Abdel H, Sayed A, Ibrahim YA (1988) Reinvestigation of the reactions of thiasemicarbazones with maleimides. Sulfur Lett 8:43Google Scholar
Beheshtia YS, Khorshidi M, Heravi MM, Baghernejad B (2010) DABCO as an efficient catalyst for the synthesis of 3-cyano-2(1H)-pyridinones and their 2-imino analogues. Eur J Chem 1:232–235CrossRefGoogle Scholar
Blokzij W, Blandamer MJ, Engberts JB (1991) Diels-Alder reactions in aqueous solution. J Am Chem Soc 113:4241–4246CrossRefGoogle Scholar
Cheng S, Comer DD (2002) An alumina-catalyzed Michael addition of mercaptans to N-anilinomaleimides and its application to the solution-phase parallel synthesis of libraries. Tetrahedron Lett 43:1179–1181CrossRefGoogle Scholar
Dhorajiya BD, Ibrahim AS, Badria FA, Dholakiya BZ (2014) Design and synthesis of novel nucleobase-based barbiturate derivatives as potential anticancer agents. Med Chem Res 23:839–847. doi:10.1007/s00044-013-0683-4CrossRefGoogle Scholar
El-Gazzar AB, Youssef MM, Abu-Hashem AA, Badria FA (2009) Design and synthesis of azolopyrimidoquinolines, pyrimidoquinazolines as anti-oxidant, anti-inflammatory and analgesic activities. Eur J Med Chem 44:609–624CrossRefPubMedGoogle Scholar
Fadda AA, El-Defrawy AM, El-Hadidy SA (2012) Synthesis, cytotoxicity activity, DFT molecular modeling studies and quantitative structure activity relationship of some novel 1,8-naphthyridine derivatives. Am J Org Chem 2:87–96CrossRefGoogle Scholar
Gutterdge J, Rowley D, Halliwell B (1981) Superoxide-dependent formation of hydroxyl radicals in the presence of iron salts. Detection of ‘free’ iron in biological systems by using bleomycin-dependent degradation of DNA. Biochem J 199:263–265CrossRefGoogle Scholar
Guzel O, Terzioglu N, Çapan G, Salman A (2006) Synthesis and biological evaluation of new 5-methyl-N-(3-oxo-1-thia-4-azaspiro[4.5]-dec-4-yl)-3-phenyl-1H-indole-2-carboxamide derivatives. Arkivoc 12:98–110Google Scholar
Kasimogullari BO, Cesur Z (2004) Fused heterocycles: synthesis of some new imidazo[1,2-a]- pyridine Derivatives. Molecules 9:894–901CrossRefPubMedGoogle Scholar
Khatik GL, Kumar R, Chakraborti AK (2006) Catalyst-free conjugated addition of thiols to α, β-unsaturated carbonyl compounds in water. Org Lett 8:2433–2436CrossRefPubMedGoogle Scholar
Lissi E, Modak B, Torres R, Escobar J, Urzua A (1999) Total antioxidant potential of resinous exudates from Heliotropium Species, and a comparison of ABTS and DPPH methods. Free RadicRes 30:471–477CrossRefGoogle Scholar
Mikhaeil BR, Badria FA, Maatooq GT, Amer MA (2004) Antioxidant and immunomodulatory constituents of Henna Leaves. Z Naturforsch 59:468–476Google Scholar
Morimoto Y, Tanaka K, Iwakiri Y, Tokuhiro S, Fukushima S, Takeuchi Y (1995) Protective effects of some neutral amino acids against hypotonic hemolysis. Biol Pharm Bull 18:1417–1422CrossRefPubMedGoogle Scholar
Pastor DS, Hessel TE, Odorisio AP, Spivack DJ (1985) 3-(4-Hydroxy-phenylthio)pyrroidine-2,5-diones. J Heterocycl Chem 22:1195CrossRefGoogle Scholar
Wabnitz TC, Yu J-Q, Spencer JB (2003) A general, polymer-supported acid catalyzed hetero-Michael addition. Synlett 7:1070Google Scholar
Zahouily M, Abrouki Y, Rayadh A, Sebti S, Dhimane H, David M (2003) Fluorapatite: efficient catalyst for the Michael addition. Tetrahedron Lett 44:2463–2465CrossRefGoogle Scholar