2′,4′-Dihydroxy-6′‑methoxy-3′,5′-dimethylchalcone and its amino acid-conjugated derivatives induce G0/G1 cell cycle arrest and apoptosis via BAX/BCL2 ratio upregulation and in silico insight in SiHa cell lines

• DOI: 10.1016/j.ejps.2023.106390
• Publication Date: 2023-02-20T17:52:06Z
• Authors: Kraikrit Utama; Nopawit Khamto; Puttinan Meepowpan; Paitoon Aobchey; Jiraporn Kantapan; Jomkhwan Meerak; Sittiruk Roytrakul; Padchanee Sangthong
• Keywords: HeLa

We modified the chemical structure of 2',4'-dihydroxy-6'‑methoxy-3',5'-dimethylchalcone (DMC, 1), a phytochemical found in seed Syzygium nervosum A.Cunn. ex DC., by conjugation with amino acid L-alanine (compound 3a) or L-valine 3b) to enhance anticancer activity and water solubility. Compounds 3a 3b had antiproliferative human cervical cancer cell lines (C-33A, SiHa HeLa), half-maximal inhibitory concentrations (IC50) 7.56 ± 0.27 8.24 0.14 µM, respectively cells; these values were approximately two-fold greater than DMC. investigated biological activities compounds based on wound healing assay, cycle assay messenger RNA (mRNA) expression analysis determine possible mechanism activity. inhibited migration assay. After treatment 3b, there was an increase cells G1 phase, indicative arrest. Moreover, compound showed potential upregulating TP53 CDKN1A that resulted upregulation BAX downregulation CDK2 BCL2, leading apoptosis The BAX/BCL2 ratio increased after 3avia intrinsic apoptotic pathway. In silico molecular dynamics simulation binding free energy calculation shed light how DMC derivatives interact HPV16 E6 protein, viral oncoprotein associated cancer. Our findings suggest is candidate for anti-cervical drug development.