Novel 3-(pyrazol-4-yl)-2-(1H-indole-3-carbonyl)acrylonitrile Derivatives Induce Intrinsic and Extrinsic Apoptotic death Mediated P53 in HCT116 Colon Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2023 Dec 18

PMID 38110432

Authors

Magda F Mohamed

Nada S Ibrahim

Amna A Saddiq

Ismail A Abdelhamid

Affiliations

Soon will be listed here.

Abstract

A novel series of α-cyano indolylchalcones was prepared, and their chemical structures were confirmed based on the different spectral data. Among them, compound 7f was observed to be the most effective bioactive chalcone with distinguished potency and selectivity against colorectal carcinoma (HCT) with IC value (6.76 µg/mL) relative to the positive control (5 FU) (77.15 µg/mL). In a preliminary action study, the acrylonitrile chalcone 7f was found to enhance apoptotic action via different mechanisms like inhibition of some anti-apoptotic protein expression, regulation of some apoptotic proteins, production of caspases, and cell cycle arrest. All mechanisms suggested that compound 7f could act as a professional chemotherapeutic agent. Also, a molecular docking study was achieved on some selected proteins implicated in cancer (Caspase 9, XIAP, P53 mutant Y220C, and MDM2) which showed variable interactions with compound 7f with good Gibbs free energy scores.

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References

Plass C, Pfister S, Lindroth A, Bogatyrova O, Claus R, Lichter P . Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet. 2013; 14(11):765-80. DOI: 10.1038/nrg3554. View

Shiri M . Indoles in multicomponent processes (MCPs). Chem Rev. 2012; 112(6):3508-49. DOI: 10.1021/cr2003954. View

Zhang D, Song H, Qin Y . Total synthesis of indoline alkaloids: A cyclopropanation strategy. Acc Chem Res. 2011; 44(6):447-57. DOI: 10.1021/ar200004w. View

Scribner A, Moore 3rd J, Ouvry G, Fisher M, Wyvratt M, Leavitt P . Synthesis and biological activity of anticoccidial agents: 2,3-diarylindoles. Bioorg Med Chem Lett. 2009; 19(5):1517-21. DOI: 10.1016/j.bmcl.2009.01.001. View

Cover C, Hsieh S, Cram E, Hong C, Riby J, Bjeldanes L . Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res. 1999; 59(6):1244-51. View

Solomon V, Hu C, Lee H . Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach. Bioorg Med Chem. 2010; 18(4):1563-72. DOI: 10.1016/j.bmc.2010.01.001. View

Tarleton M, Dyson L, Gilbert J, Sakoff J, McCluskey A . Focused library development of 2-phenylacrylamides as broad spectrum cytotoxic agents. Bioorg Med Chem. 2012; 21(1):333-47. DOI: 10.1016/j.bmc.2012.10.003. View

Kim H, Kim Y, Doddareddy M, Seo S, Rhim H, Tae J . Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers. Bioorg Med Chem Lett. 2006; 17(2):476-81. DOI: 10.1016/j.bmcl.2006.10.042. View

Chiyanzu I, Clarkson C, Smith P, Lehman J, Gut J, Rosenthal P . Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorg Med Chem. 2005; 13(9):3249-61. DOI: 10.1016/j.bmc.2005.02.037. View

10.

Radwan M, Ragab E, Sabry N, El-Shenawy S . Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents. Bioorg Med Chem. 2007; 15(11):3832-41. DOI: 10.1016/j.bmc.2007.03.024. View

11.

Lamotte Y, Martres P, Faucher N, Laroze A, Grillot D, Ancellin N . Synthesis and biological activities of novel indole derivatives as potent and selective PPARgamma modulators. Bioorg Med Chem Lett. 2010; 20(4):1399-404. DOI: 10.1016/j.bmcl.2009.12.107. View

12.

Abdellatif K, Lamie P, Omar H . 3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. J Enzyme Inhib Med Chem. 2015; 31(2):318-24. DOI: 10.3109/14756366.2015.1022174. View

13.

Lamie P, Ali W, Bazgier V, Rarova L . Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study. Eur J Med Chem. 2016; 123:803-813. DOI: 10.1016/j.ejmech.2016.08.013. View

14.

Zhang F, Zhao Y, Sun L, Ding L, Gu Y, Gong P . Synthesis and anti-tumor activity of 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives in vitro. Eur J Med Chem. 2011; 46(7):3149-57. DOI: 10.1016/j.ejmech.2011.03.055. View

15.

Venkat Ragavan R, Vijayakumar V, Suchetha Kumari N . Synthesis and antimicrobial activities of novel 1,5-diaryl pyrazoles. Eur J Med Chem. 2010; 45(3):1173-80. DOI: 10.1016/j.ejmech.2009.12.042. View

16.

Tewari A, Singh V, Yadav P, Gupta G, Singh A, Goel R . Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorg Chem. 2014; 56:8-15. DOI: 10.1016/j.bioorg.2014.05.004. View

17.

Pathak V, Maurya H, Sharma S, Srivastava K, Gupta A . Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents. Bioorg Med Chem Lett. 2014; 24(13):2892-6. DOI: 10.1016/j.bmcl.2014.04.094. View

18.

Ali A, El-Bendary E, Ghaly M, Shehata I . Synthesis, in vitro anticancer evaluation and in silico studies of novel imidazo[2,1-b]thiazole derivatives bearing pyrazole moieties. Eur J Med Chem. 2014; 75:492-500. DOI: 10.1016/j.ejmech.2013.12.010. View

19.

Sangani C, Makawana J, Zhang X, Teraiya S, Lin L, Zhu H . Design, synthesis and molecular modeling of pyrazole-quinoline-pyridine hybrids as a new class of antimicrobial and anticancer agents. Eur J Med Chem. 2014; 76:549-57. DOI: 10.1016/j.ejmech.2014.01.018. View

20.

Dawood K, Eldebss T, El-Zahabi H, Yousef M, Metz P . Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. Eur J Med Chem. 2013; 70:740-9. DOI: 10.1016/j.ejmech.2013.10.042. View