Benzo[e]pyrimido[5,4-b][1,4]diazepin-6(11H)-one derivatives as Aurora A kinase inhibitors: LQTA-QSAR analysis and detailed systematic validation of the developed model.

Aurora kinases are sub-divided into Aurora A, Aurora B, and Aurora C kinases that are considered as prospective targets for a new class of anticancer drugs. In this work, a 4-D-QSAR model using an LQTA-QSAR approach with previously reported 31 derivatives of benzo[e]pyrimido[5,4 -b][1,4]diazepin -6(11H)-one as potent Aurora kinase A inhibitors has been created. Instead of single conformation, the conformational ensemble profile generated for each ligand by using trajectories and topology information retrieved from molecular dynamics simulations from GROMACS package were aligned and used for the calculation of intermolecular interaction energies at each grid point. The descriptors generated on the basis of these Coulomb and Lennard-Jones potentials as independent variables were used to perform a PLS analysis using biological activity as dependent variable. A good predictive model was generated with nine field descriptors and five latent variables. The model showed [Formula: see text]; [Formula: see text] and [Formula: see text]. This model was further validated systematically by using different validation parameters. This 4D-QSAR model gave valuable information to recognize features essential to adapt and develop novel potential Aurora kinase inhibitors.

Role of oral amino acid supplementation in intra-uterine growth restriction and its outcome.

To compare the perinatal outcome in intra-uterine growth restriction (IUGR) with or without oral amino acid supplementation, a randomised control trial was conducted. Out of 50 mothers having IUGR, 25 received amino acid supplementation, treated as cases (group I) and rest 25 mothers with IUGR who had not received amino acid supplementation treated as controls (group II). The outcome of this study is compared in respect of (a) period of gestation at the time of delivery, (b) birth weight, (c) Apgar score, (d) neonatal intensive care unit (NICU) admission. In group I 88% continued pregnancy beyond 36 weeks and in comparison 48% delivered in between 34 and 36 weeks in group II. In group I 80% babies had birth weight between 2.5 and < 3kg, in comparison 84% babies weighing between 2 and < 2.5kg in group II. Eighty per cent of babies having Apgar score in between 7 and 10 in group I and 92% of group I cases not required any NICU admission. Oral amino acid supplementation commencing from second trimester of pregnancy significantly improves the perinatal outcome in IUGR cases.