Abstract
A new series of (E)-3-[(1-aryl-9H-pyrido[3,4-b]indol-3-yl)methylene]indolin-2-one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT-15, HCT-116, A549, NCI-H460, and MCF-7, including HFL. Among the tested compounds, (E)-1-benzyl-5-bromo-3-{[1-(2,5-dimethoxyphenyl)-9H-pyrido[3,4-b]indol-3-yl]methylene}indolin-2-one (10 s) showed potent cytotoxicity against HCT-15 cancer cells with an IC50 value of 1.43±0.26 μm and a GI50 value of 0.89±0.06 μm. Notably, induction of apoptosis by 10 s on the HCT-15 cell line was characterized by using different staining techniques, such as acridine orange/ethidium bromide (AO/EB) and DAPI. Further, to understand the mechanism of anticancer effects, various assays such as annexin V-FITC/PI, DCFDA, and JC-1were performed. The flow cytometric analysis revealed that compound 10 s arrests the HCT-15 cancer cells at the G0/G1 phase of the cell cycle. Additionally, western blot analysis indicated that treatment of 10 s on HCT-15 cancer cells led to decreased expression of anti-apoptotic Bcl-2 and increased protein expression of both pro-apoptotic Bax and caspase-3, -8, and -9, and cleaved PARP with reference to act...Continue Reading
References
Jan 1, 1964·Advances in Heterocyclic Chemistry·R A Abramovitch, I D Spenser
Jul 3, 1998·Journal of Medicinal Chemistry·L SunC Tang
Aug 7, 1999·The Journal of Biological Chemistry·A H BoularesM Smulson
May 7, 2002·Nature Reviews. Cancer·Laurence H Hurley
Feb 22, 2003·Nucleic Acids Research·Claudia TemperiniGiovanni Ughetto
Mar 11, 2003·The Journal of Pharmacology and Experimental Therapeutics·Jianguo MaJames M Gallo
Mar 21, 2003·Journal of Medicinal Chemistry·Li SunCho Tang
Jun 26, 2003·Bioorganic & Medicinal Chemistry Letters·Alfredo C CastroJulian Adams
Aug 31, 2004·Journal of Natural Products·Karumanchi V RaoMark T Hamann
Sep 24, 2005·Current Medicinal Chemistry·Georgi MomekovMargarita Karaivanova
Jan 24, 2006·Microbiological Research·Rainer-B Volk, Franz H Furkert
Feb 20, 2007·Current Medicinal Chemistry·Rihui CaoAnlong Xu
Mar 21, 2007·Biochemical and Biophysical Research Communications·Robert Roskoski
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Jun 16, 2007·Bioorganic & Medicinal Chemistry Letters·John I TrujilloDavid B Reitz
Jul 14, 2007·Current Medicinal Chemistry·Cláudio Viegas-JuniorCarlos Alberto Manssour Fraga
Apr 24, 2008·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Judith JiménezRosario Rodríguez-Arnaiz
Nov 20, 2008·The FEBS Journal·Anne SeifertPaul R Clarke
Oct 2, 2009·Carcinogenesis·S J MoghaddamBurton F Dickey
Oct 3, 2009·The FEBS Journal·Nora GöcklerWalter Becker
Oct 27, 2009·Cancer Biology & Therapy·Jing ZhangShuyi Si
Dec 1, 2009·Bioorganic & Medicinal Chemistry Letters·Paul A BarsantiAnnette O Walter
Jan 5, 2010·Free Radical Biology & Medicine·Magdalena L Circu, Tak Yee Aw
Jul 16, 2010·Bioorganic & Medicinal Chemistry Letters·Zhiyong ChenWenlie Peng
Aug 19, 2010·European Journal of Medicinal Chemistry·Zhiyong ChenHuacan Song
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Oct 16, 2012·International Journal of Oncology·Jin-Chul AhnPhil-Sang Chung
May 2, 2013·Medicinal Research Reviews·Jia ShengZhen Huang
Oct 12, 2013·ChemMedChem·Ahmed KamalSrigiridhar Kotamraju
Jan 29, 2014·ChemMedChem·Ahmed KamalNarayana Nagesh
Apr 10, 2014·ChemMedChem·Ahmed KamalNishant Jain
Mar 17, 2015·Bioorganic Chemistry·Nagula ShankaraiahAhmed Kamal
Aug 13, 2015·Bioorganic & Medicinal Chemistry·Ahmed KamalNarayana Nagesh
Dec 15, 2015·Bioorganic Chemistry·Nagula ShankaraiahAhmed Kamal
Jul 28, 2016·European Journal of Medicinal Chemistry·Pankaj SharmaNagula Shankaraiah
Jan 1, 2015·Cell Death Discovery·X LiY Li
Aug 28, 2016·Bioorganic & Medicinal Chemistry Letters·Jennifer M GiuliettiSeann P Mulcahy
Jan 6, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 27, 2017·Current Medicinal Chemistry·Shalini NekkantiNagula Shankaraiah
Jun 26, 2017·Nanomedicine : Nanotechnology, Biology, and Medicine·Anjali JainWahid Khan
Sep 20, 2017·European Journal of Medicinal Chemistry·Jincan ChenLanmei Chen
Nov 14, 2017·European Journal of Medicinal Chemistry·Jeshma KovvuriAhmed Kamal
Jan 1, 2018·European Journal of Medicinal Chemistry·Manda SathishAhmed Kamal
Citations
Jul 30, 2019·Nanomedicine·Shrikant KirwaleChandraiah Godugu
Nov 2, 2019·ChemMedChem·Chetna JadalaAhmed Kamal
Jun 6, 2019·Beilstein Journal of Organic Chemistry·Edorta Martínez de MarigortaFrancisco Palacios
Aug 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xiaofei ChenJie Zhang
Dec 18, 2019·Journal of Cellular Physiology·Sowjanya ThatikondaChandraiah Godugu
Mar 12, 2020·Organic & Biomolecular Chemistry·Darshana BoraNagula Shankaraiah
Aug 17, 2019·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Nagula ShankaraiahRamya Tokala
Oct 13, 2020·Organic & Biomolecular Chemistry·Akash P SaklaNagula Shankaraiah
Dec 1, 2020·Journal of Biomolecular Structure & Dynamics·Taoufik AkabliFatima Lamchouri
Feb 3, 2020·Bioorganic Chemistry·Liang GuoBin Dai
Feb 19, 2021·European Journal of Medicinal Chemistry·Darshana BoraNagula Shankaraiah
Oct 20, 2020·Bioorganic Chemistry·Sangita Dattatray ShindeNagula Shankaraiah
Oct 23, 2020·Bioorganic Chemistry·Ramya TokalaNagula Shankaraiah
Jun 27, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yogesh Mahadu KhetmalisKondapalli Venkata Gowri Chandra Sekhar
Jun 15, 2021·RSC Medicinal Chemistry·Jay Prakash SoniNagula Shankaraiah
Jun 28, 2021·Bioorganic & Medicinal Chemistry·Dilep Kumar SigalapalliNeelima D Tangellamudi
Aug 1, 2021·European Journal of Medicinal Chemistry·Bo Luo, Xinqiang Song