Design and Synthesis of DNA-Interactive β-Carboline-Oxindole Hybrids as Cytotoxic and Apoptosis-Inducing Agents

ChemMedChem
Ramya TokalaNagula Shankaraiah

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
May 7, 2002·Nature Reviews. Cancer·Laurence H Hurley
Jun 26, 2003·Bioorganic & Medicinal Chemistry Letters·Alfredo C CastroJulian Adams
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
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
Oct 2, 2009·Carcinogenesis·S J MoghaddamBurton F Dickey
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
May 2, 2013·Medicinal Research Reviews·Jia ShengZhen Huang
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

❮ Previous
Next ❯

Citations

Jul 30, 2019·Nanomedicine·Shrikant KirwaleChandraiah Godugu
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
Feb 19, 2021·European Journal of Medicinal Chemistry·Darshana BoraNagula Shankaraiah
Oct 20, 2020·Bioorganic Chemistry·Sangita Dattatray ShindeNagula 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
Aug 1, 2021·European Journal of Medicinal Chemistry·Bo Luo, Xinqiang Song

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.