Lead Anticancer Agents of Crinine Alkaloids: Cytotoxic, Caspase-3, and Anti-angiogenic Exploration

Several alkaloids with anticancer activities have been reported among the Crinum species. In this study, an in silico screening of crinine alkaloids was carried out to identify potential Caspase-3 activators and anti-angiogenic compounds. Thirty-one (31) crinine alkaloids were assessed for drug-likeness using the SwissADME online Web server. Nine (9) alkaloids, satisfying Lipinski’s rules for drug-likeness were selected and screened in silico for cytotoxic properties against cancer and normal cell lines using the Cell Line Cytotoxity Predictor (CLC-Pred). The alkaloids possessing drug-like properties and showing good selectivity towards cancer cell lines were evaluated for Caspase-3 activating and anti-angiogenic activities by docking with the Caspase-3 and VEGFR2 proteins, respectively. The binding energy of the compounds was compared with those of the standard drugs. Powelline, augustine, and undulatine possess drug-like properties and demonstrated good selectivity against lung cancer (A549) and oligodendroglioma (Hs683) cell lines. Among these three compounds, powelline had the best potential as a Caspase-3 stimulant and anti-angiogenic agent. Powelline, augustine, and undulatine are potential lead anticancer agents against human lung cancer and oligodendroglioma.