In vitro and in silico studies of Neophytadiene; a diterpene isolated from Aeschynomene elaphroxylon (Guill. &Perr.) Taub. as apoptotic inducer

Aeschynomene elaphroxylon (Guill. & Perr.) Taub. is a large aquatic shrub native to Madagascar and tropical Africa and cultivated in Egypt. Petroleum ether extract showed remarkable cytotoxic activities against human lung carcinoma (A-549), and prostate carcinoma cells (PC-3) with IC50 values 12.3±0.8 and 23.8±1.2 μg/ml, respectively. So, pet. ether extract was furtherly fractionated affording seven fractions, tested for cytotoxic activity against A-549, and PC-3. The sub-fraction (PET-5) from pet. ether fraction showed potent cytotoxic activities more than cisplatin against A-549, and PC-3 with IC50 values 6.94±0.48 and 7.33±0.58 µg/ml, respectively. The major compound of sub-fraction PET-5 was identified by GCMS as Neophytadiene (1) at percentage of 82.23 %. In silico studies showed that neophytadiene blocks three receptors which have main role in cancer viability, invisibility as it blocks Human A2a receptor at adenosine binding site, Human LRH1 and hERG K+ channel leads to inhibition of cancer proliferation and invasiveness which may act as a promising apoptotic inducer. The phytochemical investigation of the plant major fractions resulted in isolation of five compounds. From pet. ether fraction (1) Neophytadiene was identified, from ethyl acetate fraction (2) Kaempferol-7-O-α-L-rhamnoside and (3) Medicarpin-3-O-β-D- glucopyranoside were isolated and from n-butanol fraction (4) kaempferol 3-O-β-D-apiofuranosyl-7-O-alpha-L-rhamnoside, (5) Kaempferol 3,7-di-O-α-L-rhamnoside were isolated.