Abstract

The in silico simulations and predictions approach in evaluation of pharmacokinetic properties of new chemical entities (NCEs) is fast becoming an acceptable trend in natural products research and drug discovery. This paper focuses on the properties of trolline with respect to its anti-inflammatory and MCF-7 breast cancer cell line growth inhibition effects and an attempt to predict physico-chemical drug-like properties in silico. The compound was isolated for the first time from aerial parts of Mirabilis jalapa and the structure was elucidated by 1D and 2D NMR, FTIR and mass spectroscopic analyses. The compound was screened for anti-inflammatory and anti-MCF-7 cell lines proliferation using chemoluminiscence oxidative burst and MTT assays respectively. Predictions on physico-chemical properties central to oral route drug administration were done using commercial software Admet predictor. Results show anti-inflammatory effects at IC₅₀ concentration of 53.8 µg/ml and 48% mortality of breast cancer cell lines at 50 µM concentration. Predictions suggest moderate solubility of 1.72 to 2.92 mg/ml across pH range of 1.6 to 6.8 in simulated solvent systems and effective jejunal permeability of 5.61 x 10^-4 cm/s. The compound was also predicted to be 60% unbound to plasma proteins and an LD₅₀ of 950 mg/kg in rats. The compound, trolline had clinically important bioactive effects, probably possess promising drug-like properties suitable for further high throughput screening.

Key words: ADMET, anti-inflammatory, in silico prediction, Mirabilis jalapa, NMR, trolline.