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Discovery of a 2,4-diphenyl-5,6-dihydrobenzo(h)quinolin-8-amine derivative as a novel DNA intercalating topoisomerase IIα poison.

التفاصيل البيبلوغرافية
العنوان: Discovery of a 2,4-diphenyl-5,6-dihydrobenzo(h)quinolin-8-amine derivative as a novel DNA intercalating topoisomerase IIα poison.
المؤلفون: Kunwar S; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Hwang SY; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, 120-750, Republic of Korea., Katila P; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Park S; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, 120-750, Republic of Korea., Jeon KH; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, 120-750, Republic of Korea., Kim D; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, 120-750, Republic of Korea., Kadayat TM; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Kwon Y; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul, 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr., Lee ES; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea. Electronic address: eslee@yu.ac.kr.
المصدر: European journal of medicinal chemistry [Eur J Med Chem] 2021 Dec 15; Vol. 226, pp. 113860. Date of Electronic Publication: 2021 Sep 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE
أسماء مطبوعة: Publication: Paris : Editions Scientifiques Elsevier
Original Publication: Paris, S.E.C.T. [etc.]
مواضيع طبية MeSH: Drug Discovery*, Amines/*pharmacology , Antineoplastic Agents/*pharmacology , DNA Topoisomerases, Type II/*metabolism , Topoisomerase II Inhibitors/*pharmacology, Amines/chemical synthesis ; Amines/chemistry ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Humans ; Molecular Structure ; Structure-Activity Relationship ; Topoisomerase II Inhibitors/chemical synthesis ; Topoisomerase II Inhibitors/chemistry ; Tumor Cells, Cultured
مستخلص: Several anticancer agents have been developed and innovative approaches have been made toward cancer type-specific medicines for cancer treatment. As a continuous effort to develop potential chemotherapeutic agents, a novel series of 2,4-diphenyl-5,6-dihydrobenzo(h)quinolin-8-amines containing amino groups, hydroxyphenyl and fluorine functionalities were designed and synthesized. The compounds were evaluated for topo IIα inhibitory and cytotoxicity against HCT15, and HeLa human cancer cell lines. Among synthesized thirty compounds, the majority exhibited strong topo IIα inhibition and anti-proliferation against HCT15 colorectal adenocarcinoma cell line. The structure-activity relationship study revealed that compounds with -CF 3 and -OCF 3 substituents at 4- position and 3' or 4'-hydroxyphenyl at 2-position attached to the central pyridine ring displayed potent topo IIα and anti-proliferative activity in colorectal and cervix cancer cell line. In vitro studies provided the evidence that compounds 16, 19, 22, and 28 possess excellent topo IIα inhibition and antiproliferative activity. For a better understanding, topo IIα cleavage complex, EtBr displacement, KI quenching assays and molecular docking of compound 19 was performed and the results revealed the mode of action as a DNA intercalative topo IIα poison inhibitor. The results obtained from this study provide insight into the DNA binding mechanism of 2,4-diphenyl-5,6-dihydrobenzo(h)quinolin-8-amines and alteration in topo IIα inhibitory and antiproliferative activity with modifications in the rigid structure.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
فهرسة مساهمة: Keywords: 2,4,6-Triarylyridines; 5,6-Dihydrobenzo(h)Quinolin-8-amine; Antiproliferative activity; Structure-activity relationship; Topo IIα poison inhibitor
المشرفين على المادة: 0 (Amines)
0 (Antineoplastic Agents)
0 (Topoisomerase II Inhibitors)
EC 5.99.1.3 (DNA Topoisomerases, Type II)
تواريخ الأحداث: Date Created: 20211001 Date Completed: 20220124 Latest Revision: 20220124
رمز التحديث: 20231215
DOI: 10.1016/j.ejmech.2021.113860
PMID: 34597897
قاعدة البيانات: MEDLINE
الوصف
تدمد:1768-3254
DOI:10.1016/j.ejmech.2021.113860