Prateek Kumar Jain

Synthesis, characterization and pharmacological evaluation of amide prodrugs of Flurbiprofen

Flurbiprofen (FB) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study was aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of FB were synthesized by amidation with ethyl esters of amino acids, namely, glycine, L-phenylalanine, L-tryptophan, L-valine, L-isoleucine, L-alanine, L-leucine, L-glutamic acid, L-aspartic acid and b alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for bioavailibility studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to FB. Among synthesized prodrugs AR-9, AR-10 and AR-2 showing excellent pharmacological response and encouraging hydrolysis rate both in (Simulated Intestinal Fluid) SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent resulted in enhanced partition coefficient but diminished dissolution and hydrolysis rate. Such prodrugs can be considered for sustained release purpose.

QSAR study on some arylsulfonamides as anti-HIV agents

In pursuit of better anti-HIV drugs, quantitative structure-activity relationship (QSAR) studies were performed on a series of aryl sulfonamide HIV protease inhibitors using Win CAChe 6.1. Multiple linear regression analysis was performed to derive QSAR models, which were further evaluated for statistical significance and predictive power by internal and external validation. The QSAR model indicates that the thermodynamic descriptors (heat of formation, log P, and molar refractivity) and steric descriptor (solvent assessable surface area) play an important role for the anti-HIV activity. The results of the present study may be useful on the designing of more potent anti-HIV agents.

Prediction of caspase-3 inhibitory activity of 1,3-dioxo-4-methyl-2,3-dihydro-1h-pyrrolo[3,4-c] quinolines: QSAR study

Neurodegenerative disorders are consequences of progressive and irreversible loss of neurons due to unwanted apoptosis which involves caspases, a group of cysteine proteases that cleave other proteins and inactivate them. Among several different groups of caspase enzymes, caspases-3 plays a key role in apoptosis and are a therapeutic target for their inhibition. In pursuit of better caspase-3 inhibitors, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c] quinolines as caspase-3 inhibitors using WIN CAChe 6.1 and Medicinal Chemistry Regression Machine. The best QSAR model was selected and validated by internal and external validation method. The values of statistical data are r = 0.955, F = 72.95, SEE = 0.397, q2 = 0.885, SPRESS = 0.44. The present study reveals that when the conformational minimum energy is increased, and lowest unoccupied molecular orbital energy and highest occupied molecular orbital energy are decreased the biological activity can be increased. On the basis of a selected QSAR model, we designed a new series of 1,3-dioxo-4-methyl-2,3-dihydro-1H-pyrrolo[3,4-c]quinolines compounds, calculated their caspases inhibitory activity and found that the designed compounds were more potent than the existing compounds.

Large choroid plexus teratoma : A rare cause of congenital hydrocephalus

Teratomas form the most common type of congenital brain tumors, frequently presenting as stillbirth. The largest neonatal series of intracranial teratomas reported a 12% survival rate. Although the first teratoma of the lateral ventricle was reported in 1961 by Maier, neonatal intracranial teratoma of the lateral ventricle is an extremely rare entity. We report here a large intracranial poorly differentiated teratoma arising from choroid plexus of lateral ventricle. This typically presented at birth with a large congenital hydrocephalus.

Calcium-silicate-based floating granular delivery system of ranitidine hydrochloride for effective management of peptic ulcer

The objective of the present investigation was to prepare and evaluate a floating granular delivery system for the treatment of mucosal ulcer consisting of (i) calcium silicate (CS) as a porous carrier; (ii) ranitidine hydrochloride (RH), an anti-ulcer agent; and (iii) hydroxypropyl methylcellulose K4M (HPMC) and ethylcellulose (EC) as matrix-forming polymers. The effect of various formulation and process variables on the particle morphology, particle size, micromeritic properties, percent drug content, in vitro floating behavior, and in vitro drug release from the floating granules was studied. Scanning electron microscopy (SEM) of the granules revealed that that more pores of CS in secondary coated granules (SCG) were covered by the polymer solution than those in primary coated granules (PCG). The formulation demonstrated favorable in vitro floating and sustained drug release characteristics. The in vivo evaluation for the determination of pharmacokinetic parameters was performed in albino rats. Higher plasma concentration was maintained throughout the study period from the floating granules of RH. The enhanced bioavailability and elimination half-life observed in the present study may be due to the floating nature of the dosage form and the reduction of the absolute alcohol-induced ulcerogenic index from 3.0 to 0.6. The results suggested that CS is a useful carrier for the development of floating and sustained release preparations.