Current Issue : April - June Volume : 2018 Issue Number : 2 Articles : 5 Articles
Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and is noticed globally. Despite\nalarming conditions, this disease lacks effective medications; however, the farnesyltransferase inhibitors (FTIs) are a hope in the\ndark. Therefore, the objective of the present article is to identify new compounds from the databases employing pharmacophore\nbased virtual screening. Utilizing nine training set compounds along with lonafarnib, a common feature pharmacophore was\nconstructed consisting of four features. The validated Hypo1 was subsequently allowed to screen Maybridge, Chembridge, and\nAsinex databases to retrieve the novel lead candidates, which were then subjected to Lipinski�s rule of 5 and ADMET for druglike\nassessment. The obtained 3,372 compounds were forwarded to docking simulations and were manually examined for the key\ninteractions with the crucial residues. Two compounds that have demonstrated a higher dock score than the reference compounds\nand showed interactions with the crucial residues were subjected to MD simulations and binding free energy calculations to assess\nthe stability of docked conformation and to investigate the binding interactions in detail. Furthermore, this study suggests that the\nHits may be more effective against progeria and further the DFT studies were executed to understand their orbital energies....
Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way\nof combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction\nwith competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of\nsixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region,\ntwo hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the bindingmodes of these inhibitors with\nPTP1B active sites, four docking programs (AutoDock 4.0,AutoDockVina 1.0, standard precision (SP)Glide 9.7, and extra precision\n(XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results.\nIn conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship\n(SAR) can be used to design novel potent PTP1B inhibitors....
After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their\nstiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs\nresulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of\nthe female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective\nvolume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smoothmuscle (5%) is adopted to characterize\nthe mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of\neach fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite\nelement simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A\nsignificant dislocation of the urethrovesical junction is observed due toweakness of the fascia (13.89 mm)compared to the ligaments\n(5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder\nhyper mobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females....
Breast cancer is one of the leading causes of death noticed in women across the world. Of late the most successful treatments\nrendered are the use of aromatase inhibitors (AIs). In the current study, a two-way approach for the identification of novel leads\nhas been adapted. 81 chemical compounds were assessed to understand their potentiality against aromatase along with the four\nknown drugs.Docking was performed employing theCDOCKER protocol available on the Discovery Studio (DS v4.5). Exemestane\nhas displayed a higher dock score among the known drug candidates and is labeled as reference. Out of 81 ligands 14 have\nexhibited higher dock scores than the reference. In the second approach, these 14 compounds were utilized for the generation of the\npharmacophore.The validated four-featured pharmacophore was then allowed to screen Chembridge database and the potential\nHits were obtained after subjecting them to Lipinski�s rule of five and the ADMET properties. Subsequently, the acquired 3,050\nHits were escalated tomolecular docking utilizing GOLD v5.0. Finally, the obtained Hits were consequently represented to be ideal\nlead candidates that were escalated to the MD simulations and binding free energy calculations. Additionally, the gene-disease\nassociation was performed to delineate the associated disease caused by CYP19A1....
Human aromatase (CYP19A1) is an important enzyme, which produces estrogen from androgen for maintaining the female\nreproductive function and pregnancy. Triclocarban and triclosan are antimicrobial chemicals added to personal care, household,\nand industrial products. They could be endocrine disruptors and may disrupt human CYP19A1 activity. In the present study,\nwe investigated the effects of triclocarban and triclosan on estradiol production and human CYP19A1 activity in JEG-3 cells.\nTriclocarban and triclosan reduced estradiol production in JEG-3 cells. Triclocarban and triclosan inhibited human CYP19A1 with\nIC50 values of 15.81 and 6.26 ...
Loading....