Exploring the antioxidant and antiproliferative properties of Flacourtia indica Extracts on lung cancer cells: A comprehensive analysis utilizing GC-MS, molecular docking, and PASS analysis

The study aimed to explore the antiproliferative potential against a lung cancer cell line for the first time, alongside investigating phytochemical composition, antioxidant activity, and conducting GC-MS analysis of Flacourtia indica extracts. This was supplemented by in silico molecular docking, simulation and PASS (Prediction of Activity Spectra for Substances) prediction study for selected compounds. The leaves of the plant were extracted with n-hexane, chloroform, and methanol in order of polarity and the phyto-constituents were determined by GC-MS spectroscopy techniques. Trypan blue exclusion assay was used to measure lung cancer cell line viability to determine extract's antiproliferative effect. Alongside this cytotoxic effect of the extracts was also carried out by brine shrimp lethality test. The phenolic, flavonoid, antioxidant content analysis was carried out by spectroscopic method. Molecular docking analysis further assessed the binding affinity of these bioactive compounds with proteins including topoisomerase II, calvasculin, porin, and TP53 and RMSD, RMSF, radious of gyration and solvent accessible surface area were calculated by molecular simulation. GC-MS analysis of crude chloroform extract revealed Cyclopropanepentanoic acid, 2-undecyl-, methyl ester (13.072%), phytol (12.667%), benzene,1,2,4-trimethyl, decane, pentadecanoic acid,14-methyl, and 9,12-Octadecanoic acid, methyl ester, and 20 other components. Total phenolics and flavonoids in crude chloroform extract are 2.3882 ± 1.47 mg/gm Gallic acid equivalent and 126.246±4.252 mg/gm quercetin equivalent. The crude chloroform extract (CCE) has antioxidant properties, with IC 50 values of 38.691±0.582 µg/mL for DPPH scavenging and 59.81±0.272 µg/mL for iron reducing methods, and 148.75±1.25 mg/gm for catechin antioxidants. The in silico PASS prediction analysis of the prominent compounds was also carried out against different cell line of lung cancer. The Pa value ranges from 0.502 to 0.639 revealed considerable antiproliferative activity of the constituents. Compared to tamoxifen as positive control, crude chloroform extract (CCE) inhibited lung-cancer cell proliferation by 22.87%. Molecular docking and simulation studies identified chemical compounds that interact with cancer biomarker proteins, supporting the anti-carcinogenic findings observed in wet lab experiments. This comprehensive study provides valuable insights into the anti-carcinogenic potential of Flacourtia indica extracts, particularly against lung cancer cell lines. Further research is warranted to explore its therapeutic potential and pave the way for the development of novel anti-cancer agents derived from natural sources