Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from and : Evidence from In Silico Target Fishing and In Vitro Testing.

Roem. & Schult and resin of (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., - from and - from Their structures were confirmed by combined spectroscopic techniques including 1D (H and C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds -, , and , which depicted IC values in the range of 35-60 μM, while , , and also demonstrated IC values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds (IC = 14.4 µM), (IC = 23.3), and (IC = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, possesses the highest antioxidant (55 μM) activity followed by (241 μM). The results indicated that compound can be a promising candidate for antioxidant drugs, while compound is a potential candidate for anticancer drugs.