Novel Chrysin-De-Allyl PAC-1 Hybrid Analogues as Anticancer Compounds: Design, Synthesis, and Biological Evaluation

被引：9

作者：

Al-Oudat, Buthina A. ^{[1
]}

Ramapuram, Hariteja ^{[2
]}

Malla, Saloni ^{[2
]}

Audat, Suaad A. ^{[3
]}

Hussein, Noor ^{[2
]}

Len, Jenna M. ^{[2
]}

Kumari, Shikha ^{[4
]}

Bedi, Mel F. ^{[5
]}

Ashby, Charles R., Jr. ^{[6
]}

Tiwari, Amit K. ^{[2
]}

机构：

[1] Jordan Univ Sci & Technol, Dept Med Chem & Pharmacognosy, Fac Pharm, POB 3030, Irbid 22110, Jordan

[2] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol & Expt Therapeut, Toledo, OH 43614 USA

[3] Jordan Univ Sci & Technol, Coll Sci & Arts, Dept Chem, POB 3030, Irbid 22110, Jordan

[4] Univ Nebraska Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA

[5] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Med & Biol Chem, Toledo, OH 43614 USA

[6] St Johns Univ, Coll Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Queens, NY 11439 USA

来源：

MOLECULES | 2020年 / 25卷 / 13期

关键词：

triple-negative breast cancer; cytotoxicity; chrysin analogues; flavonoid; anticancer compounds; ANTITUMOR-ACTIVITY EVALUATION; CASPASE ACTIVATION; INDUCED APOPTOSIS; CANCER; FLAVONOIDS; DERIVATIVES; MECHANISMS; BCL-2; INHIBITION; AGENTS;

D O I：

10.3390/molecules25133063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (4a-4o), were rationally designed and synthesized. The target compounds were screened for in vitro antiproliferative efficacy in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231, and normal human mammary epithelial cells (HMECs). Two compounds,4gand4i, had the highest efficacy and selectivity towards MDA-MB-231 cells, and thus, were further evaluated by mechanistic experiments. The results indicated that both compounds4gand4iinduced apoptosis by (1) inducing cell cycle arrest at the G2 phase in MDA-MB-231 cells, and (2) activating the intrinsic apoptotic pathways in a concentration-dependent manner. Physicochemical characterizations of these compounds suggested that they can be further optimized as potential anticancer compounds for TNBC cells. Overall, our results suggest that4gand4icould be suitable leads for developing novel compounds to treat TNBC.

引用

页数：20

共 62 条

[1] Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats [J].