Evaluation of reversible contraceptive potential of Cordia dichotoma leaves extract

Considering the safety-risk ratio of steroidal contraceptives, the present work was carried out to evaluate ethno-contraceptive use of Cordia dichotoma G. Forst., Boraginaceae, leaves (LCD). Preliminary pharmacological screening was performed on post-coital female albino rats. The leaves extract (LD50 5.50 g/kg bw) showed 100% anti-implantation activity (n=10) at 800 mg/kg dose level. (2-hydroxypropyl)-β-cyclodextrin (BCD) was used as bioavailability enhancer to form LCD-BCD complex, characterized by DLS, SEM and XRD analyses. The LCD-BCD complex (1:1, w/w) exhibited 100% pregnancy interception (n=20) at the dose level of 250 mg/kg and also showed strong estrogenic potential with a luteal phase defect. Qualitative and quantitative phytochemical analyses were carried out. The LCD extract was standardized by a validated HPTLC method and two contraceptive phytoconstituents, apigenin and luteolin were isolated. A detailed pharmacological analyses followed by chronic toxicity study were performed to predict the reversible nature of the developed phytopharmaceutical. The histological and biochemical estimations detected the reversible contraceptive potential after withdrawal. The observations suggested that the developed phyto-pharmaceutical has potential antifertility activity with safety aspects.

Molecular mapping of heterocyclic diazene derivatives for estrogen receptor modulation.

Selective estrogen receptor modulators (SERMs) are effectively used in hormone replacement therapy (HRT) by reducing post-menopausal symptoms, including hormone-responsive breast cancer and osteoporosis. The present study explored the pharmacophore features of diazene derivatives for selective estrogen receptor (ER) modulation using quantitative structure activity relationship (QSAR) and space modeling approaches. The 2D-QSAR models (R2α = 0.907, Q2α = 0.700, R2pred-α = 0.735; R2β = 0.913, Q2β = 0.756, R2pred-β = 0.745) showed the importance of orbital energies, hydrophobicity, refractivity and atomic charges for selective binding affinity to ER. In 3D-QSAR, molecular field (CoMFA, R2α = 0.948, Q2 = 0.720, R2pred-α = 0.708; R2β = 0.994, Q2β = 0.541, R2pred-β = 0.721) and similarity models (CoMSIA, R2α = 0.984, Q2α = 0.793, R2pred-α = 0.738; R2β = 0.996, Q2β = 0.681, R2pred-β = 0.725) indicated that steric and hydrophobic properties were important for binding selectivity. Space modeling study (R2α = 0.885, Q2α = 0.855, R2pred-α = 0.666; R2β = 0.872, Q2β = 0.883, R2pred-β = 0.814) revealed that hydrophobic and aromatic ring features were important for both subtypes, whereas hydrogen bond (HB) acceptor and donor were crucial for β- and α-subtypes, respectively. Interactions observed between ligand and catalytic residues at the active site in docking study substantiated the developed model which may be successfully used in high throughput screening (HTS) to obtain promising lead molecules for selective estrogen therapy.