Multitarget Mechanisms of Monocarbonyl Curcuminoid Analogues against HL-60 Cancer Cells: <i>In Vitro</i> and Network Pharmacology-Based Approach
Aisha Rahman, Fatima Noor, Usman Ali Ashfaq, Hany W. Darwish, Michael Aschner, Zia Ud Din, Haroon Khan
Abstract
High Resolution Image Download MS PowerPoint Slide This study addressed the cytotoxic potential of four compounds: monocarbonyl curcuminoid, ethyl (2E)-2-benzylidene-3-oxobutanoate 1, 1,2-dimethoxy-12-methyl-13H- [1,3] benzodioxolo[5,6- c ] phenanthridine 2, 3,5-dibenzyloxybenzyl bromide 3, and (E)-4-(4-chlorobenzylidene)-1-(4-nitrophenyl)hexan-3-one 4 . In vitro cytotoxic assays were carried out in HL-60 and BJ cells using the MTT assay along with analysis of apoptosis with the annexin V detection kit. Additional network pharmacology and docking analyses were carried out. In the in vitro assays, compounds 2 and 4 displayed significant antiproliferative effects in HL-60 cells, exhibiting IC 50 values of 5.02 and 9.50 μM, respectively. Compound 1 showed no activity, and compound 3 displayed toxicity in BJ cells. In addition, both compounds 2 and 4 induced apoptosis in HL-60 cells. Network pharmacology and docking analyses indicated that compounds 2 and 4 had synergistic effects targeting the CASP3 and PARP1 proteins. Notably, these proteins play pivotal roles in cancer-related pathways. Thus, by modulating these proteins, monocarbonyl curcuminoid has the potential to influence various cancer-related pathways. In summary, our novel findings provide valuable insights into the potential of these compounds to serve as novel anticancer therapeutic agents, warranting further mechanistic studies and clinical exploration.