Cytotoxic activity of quinolinequinones in cancer: In vitro studies, molecular docking, and ADME/PK profiling


JANNUZZI A. T., YILMAZ GÖLER A. M., Shilkar D., Mondal S., Basavanakatti V. N., Yildirim H., ...More

CHEMICAL BIOLOGY & DRUG DESIGN, vol.102, no.5, pp.1133-1154, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 102 Issue: 5
  • Publication Date: 2023
  • Doi Number: 10.1111/cbdd.14314
  • Journal Name: CHEMICAL BIOLOGY & DRUG DESIGN
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1133-1154
  • Keywords: ADME, anticancer activity, breast cancer, cytotoxicity, leukemia, molecular docking
  • Istanbul University Affiliated: Yes

Abstract

Lead molecules containing 1,4-quinone moiety are intriguing novel compounds that can be utilized to treat cancer owing to their antiproliferative activities. Nine previously reported quinolinequinones (AQQ1-9) were studied to better understand their inhibitory profile to produce potent and possibly safe lead molecules. The National Cancer Institute (NCI) of Bethesda chose all quinolinequinones (AQQ1-9) based on the NCI Developmental Therapeutics Program and tested them against a panel of 60 cancer cell lines. At a single dose and five further doses, AQQ7 significantly inhibited the proliferation of all leukemia cell lines and some breast cancer cell lines. We investigated the in vitro cytotoxic activities of the most promising compounds, AQQ2 and AQQ7, in MCF7 and T-47D breast cancer cells, DU-145 prostate cancer cells, HCT-116 and COLO 205 colon cancer cell lines, and HaCaT human keratinocytes using the MTT assay. AQQ7 showed particularly high cytotoxicity against MCF7 cells. Further analysis showed that AQQ7 exhibits anticancer activity through the induction of apoptosis without causing cell cycle arrest or oxidative stress. Molecular docking simulations for AQQ2 and AQQ7 were conducted against the COX, PTEN, and EGFR proteins, which are commonly overexpressed in breast, cervical, and prostate cancers. The in vitro ADME and in vivo PK profiling of these compounds have also been reported.