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Identification of new halogen-containing 2,4-diphenyl indenopyridin-5-one derivative as a boosting agent for the anticancer responses of clinically available topoisomerase inhibitors.

التفاصيل البيبلوغرافية
العنوان: Identification of new halogen-containing 2,4-diphenyl indenopyridin-5-one derivative as a boosting agent for the anticancer responses of clinically available topoisomerase inhibitors.
المؤلفون: Hwang SY; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Shrestha A; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Park S; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Bist G; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Kunwar S; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Kadayat TM; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea., Jang H; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Seo M; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Sheen N; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Kim S; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Jeon KH; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea., Lee ES; College of Pharmacy, Yeungnam University, Gyeongsan, 38541, Republic of Korea. Electronic address: eslee@yu.ac.kr., Kwon Y; College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
المصدر: European journal of medicinal chemistry [Eur J Med Chem] 2022 Jan 05; Vol. 227, pp. 113916. Date of Electronic Publication: 2021 Oct 11.
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: Antineoplastic Agents/*pharmacology , DNA Topoisomerases, Type I/*metabolism , DNA Topoisomerases, Type II/*metabolism , Halogens/*pharmacology , Indenes/*pharmacology , Poly-ADP-Ribose Binding Proteins/*metabolism , Pyridones/*pharmacology , Topoisomerase Inhibitors/*pharmacology, Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; DNA/chemistry ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Female ; Halogens/chemistry ; Humans ; Indenes/chemical synthesis ; Indenes/chemistry ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Structure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Pyridones/chemical synthesis ; Pyridones/chemistry ; Structure-Activity Relationship ; Topoisomerase Inhibitors/chemical synthesis ; Topoisomerase Inhibitors/chemistry ; Tumor Cells, Cultured
مستخلص: Based on previous reports on the significance of halogen moieties and the indenopyridin-5-one skeleton, we designed and synthesized a novel series of halogen (F-, Cl-, Br-, CF 3 - and OCF 3 -)-containing 2,4-diphenyl indenopyridin-5-ones and their corresponding -5-ols. Unlike indenopyridin-5-ols, most of the prepared indenopyridin-5-ones with Cl-, Br-, and CF 3 - groups at the 2-phenyl ring conferred a strong dual topoisomerase I/IIα inhibitory effect. Among the series, para-bromophenyl substituted compound 9 exhibited the most potent topoisomerase inhibition and antiproliferative effects, which showed dependency upon the topoisomerase gene expression level of diverse cancer cells. In particular, as a DNA minor groove-binding non-intercalative topoisomerase I/IIα catalytic inhibitor, compound 9 synergistically promoted the anticancer efficacy of clinically applied topoisomerase I/IIα poisons both in vitro and in vivo, having the great advantage of alleviating poison-related toxicities.
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.)
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Halogens)
0 (Indenes)
0 (Poly-ADP-Ribose Binding Proteins)
0 (Pyridones)
0 (Topoisomerase Inhibitors)
9007-49-2 (DNA)
91080-16-9 (calf thymus DNA)
EC 5.99.1.2 (DNA Topoisomerases, Type I)
EC 5.99.1.2 (TOP1 protein, human)
EC 5.99.1.3 (DNA Topoisomerases, Type II)
EC 5.99.1.3 (TOP2A protein, human)
تواريخ الأحداث: Date Created: 20211022 Date Completed: 20220125 Latest Revision: 20220125
رمز التحديث: 20231215
DOI: 10.1016/j.ejmech.2021.113916
PMID: 34678573
قاعدة البيانات: MEDLINE
الوصف
تدمد:1768-3254
DOI:10.1016/j.ejmech.2021.113916