Molecular Docking of 4-ethoxychalcones on Oxidoreductase/Pirin Inhibitors and Cytotoxic Evaluation on Breast/Skin Cancer Cell Lines

Abstract

Background: The role of α, β unsaturated propenone derivatives has attracted the chemists for its biological importance. An attempt is made to know the interaction with breast and skin cancer cell lines along with molecular docking studies. Objective: To synthesize and characterize 4-ethoxychalcones for testing towards breast and skin cancer targets. Method: A series of chalcone analogues starting from 4-ethoxyacetophenone and substituted aromatic aldehydes were synthesized, well characterized and evaluated for their in vitro anticancer activities against human breast cancer (MDA-MB-231) and human metastatic melanoma (A-375) cell lines by MTT assay. Docking simulation was performed to know the drug-receptor interaction of chalcone scaffold on the active site of target inhibitor bound cytochrome P450 family oxidoreductase for breast cancer and pirin inhibiting target for skin cancer respectively. Result: After performing cytotoxic evaluation, it was observed that the compounds having substitution at the para position showed better results compared to ortho and meta positions for both the cell lines. Molecular docking studies revealed different types of interactions with selected oxidoreductase and pirin inhibiting targets. Ligand–protein interactions and morphological changes are monitored by molecular dynamics. Conclusion: The presence of electron withdrawing and donating groups on ring B marginally affected IC50 and docking score. The stability of the binding mode of the ligands having most inhibitory efficiency for compounds 8 and 10 predicted by docking studies were confirmed by molecular dynamics simulation. Evaluated pharmacokinetic parameters were found to be within the acceptable range. Further molecular dynamics study provided necessary information.

The Synthesis of 2′-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities

“…When compared to other reported chalcones tested on different melanoma cell lines, we found that compound 12 is two times more active than those of the ethoxy-chalcones class, studied by Harshitha et al [36], where the best derivative showed an IC 50 value of 53.47 µM for A-375 metastatic melanoma cell line. On the other hand, compound 12 was found to be less active than the synthesized chalcone-sulfonamide hybrids reported by Castaño et al [37], most of them possessing activities against LOX IMVI melanoma cell line, with IC 50 values between 0.34 and 0.54 µM.…”

Anticancer Activity of Chalcones and Its Derivatives: Review and In Silico Studies

“…Another reported class refers to ethoxychalcones; these were studied by Harshitha and collaborators (2020) [ 51 ] and were obtained by classic aldol condensation. The best compound was derivative ( 28 ) ( Figure 7 ), which showed IC50 value = 53.47 μM for breast cancer cell line MDA-MB-231 and metastatic melanoma cells (A-375).…”