Effect of (-)-epicatechin, a flavonoid on the NO and NOS activity of Raillietina echinobothrida.

(-)-Epicatechin, a natural flavonoid reportedly has huge pharmacological properties. In this study the cestocide effect of (-)-epicatechin is demonstrated in Raillietina echinobothrida. Although the antiparasitic activity of (-)-epicatechin has been demonstrated against protozoa, helminths and ectoparasites, in the present study the cestocide activity of (-)-epicatechin is shown to be related to a decrease in nitric oxide synthase (NOS) activity and nitric oxide (NO) production. On exposure to 0.53mg/ml each of epicatechin, reference drug praziquantel and Ñ  Nitro-l- Arginine Methyl Ester (NOS inhibitor), the parasites attained paralysis at 10.15, 0.27 and 11.21h followed by death at 30.15, 1.21 and 35.18h respectively. Biochemical analysis showed a significant decrease in activity of NOS (57.360, 36.040 and 44.615%) and NO (41.579, 19.078 and 24.826%) in comparison to the controls. NADPH-diaphorase histochemical staining (a selective marker for NOS in neuronal tissue) demonstrated a pronounced decline in the visible staining activity in the tegument, subtegument and the peripheral nerve regions following exposure to the treatments. Strong binding affinity of (-)-epicatechin with NOS protein was also revealed through docking studies. The results strongly define the probable anthelmintic activity of our compound through its influence on the NOS activity.

Molecular Modeling and Dynamics Simulation Analysis of KATNAL1 for Identification of Novel Inhibitor of Sperm Maturation.

BACKGROUND: Hormone based birth control often causes various side effects. A recent study revealed that temporary infertility without changing hormone levels can be attained by inhibiting Katanin p60 ATPase-containing subunit A-like 1 protein (KATNAL1) which is critical for sperm maturation in the testes. OBJECTIVE: This study aimed at attaining the most energetically stable three dimensional (3D) structure of KATNAL1 protein using comparative modeling followed by screening of a ligand library of known natural spermicidal compounds for their binding affinity with KATNAL1. This in turn may inhibit the development of mature sperm in the seminiferous epithelium. METHOD: A series of computational techniques were used for building the 3D structure of KATNAL1 which was further optimized by molecular dynamics (MD) simulation. For revealing the ATP binding mode of KATNAL1, docking study was carried out using the optimized model obtained from the MD simulation. The docking study was also employed to test the binding efficiency of the ligand library. RESULTS: Molecular docking study confirmed the ATP binding of KATNAL1 with various hydrophobic and hydrogen bond interactions. Binding efficiency of the ligand library suggested that calotropin, a cardenolide of Calotropis procera showed the highest binding efficiency against the target protein without toxicity. MD simulation of the docked complex validated the results of the docking study. CONCLUSION: This study revealed the ATP binding mode of KATNAL1 and identified calotropin as a potential lead molecule against it showing high binding efficiency with good bioavailability and no mutagenicity. Further in vitro and in vivo bioassay of calotropin could facilitate the development of novel non-hormonal male-specific contraceptive in near future.