Astellas Pharma (India)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: The immunomodulatory drugs (IMiDs) have made a profound difference in the treatment of multiple myeloma (MM). Lenalidomide (LND) is chiral compound with two enantiomers and one enantiomer may have different pharmacologic action than the other. For a given chiral drug, until proven otherwise, it is right to think of the two enantiomers as two different drugs with unique properties. Aims: This study aimed to explore efficacy of lenalidomide (R) - (+) and (S) - (-) enantiomers in human multiple myeloma cell line. Methods: H929 myeloma cell line model was designed to understand the potential differences in chirality of the R and S form of LND enantiomers and racemate in multiple myeloma cell line. We report the first biological evaluation of lenalidomide in racemic and in both (R)- and (S)-enantiomerically pure forms against (in vitro) H929 cells of multiple myeloma (MM) using an annexin V assay. Results: It was observed that at 48 hours S-LND treated cells demonstrated significant reduction in the metabolic activity at 10 and 20 µg/mL and profound morphological changes. Cell cycle analysis showed cells in S and G2/M phase were decreased suggesting that all of the drugs can arrest cells at G1 cell cycle phase. We demonstrate (S) - (-) enantiomers of lenalidomide inhibited the growth of H929 MM cells without any in-vivo activation. Summary/Conclusion: The study concludes that (S) - (-) enantiomers of lenalidomide noted more potent agent which could have both the anti-cancerous and immunomodulatory activity.Keywords: Imids, Cell line, Multiple myeloma

Antibiotic resistance represents one of the biggest challenges, and there is an urgent need for plant-based antimicrobial agents that enable managing this crisis effectively. In this work, we aimed to investigate the antibacterial activity of Astragalus candolleanus (A. candolleanus) hydromethanolic root extract against Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Kocuria rhizophila) strains by the cup-plate method. The root was powdered and extracted with 70% methanol by cold maceration for 5 days. Preliminary phytochemical screening was performed with different solvents in the order of increasing polarity. Pure compounds were isolated by column chromatography and were characterized through liquid chromatography-mass spectrometry. Targeted predictions of the isolated compounds were also studied using Swiss Target prediction software and prediction of activity spectra for substances. The extract showed a broad zone of inhibition against pathogenic bacteria. Four pure compounds were isolated, of which a novel terpenoid compound has been identified as stemmadenine along with scillirosidin, cephalotaxine, and myxoxanthophyll. The structures of the isolated phytoconstituents were elucidated by spectral analysis. The four pure components isolated from the roots of A. candolleanus are suggested to be effective against tested pathogens. Overall results of drug design suggest that myxoxanthophyll is a promising bioactive compound endowed with antibacterial activity.

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.

A simple and rapid HPLC method is developed and validated for the simultaneous determination of Flibanserin and Caffeine. This is the first single reported method for these two drugs. The good separation was achieved by HPLC technique using 0.1% ammonium acetate buffer (pH 3) and ACN as the mobile phase, a C18 column and wavelength set at 254nm. The retention time for Caffeine and Flibanserin is 2.0 min and 4.9 min respectively. The method was validated as per ICH guidelines for linearity, precision, accuracy, LOD, LOQ, robustness and solution stability. The method shows good accuracy and precision with RSD value of less than 2%. The Flibanserin shows good linearity in range 50.0g-150.0g/mL and Caffeine in range 10.0g-30.0g/ mL.

Introduction: Ocimum basilicum (OB), a herb known for its antihypertensive, anticholinesterase and antioxidant properties was investigated for possible intraocular pressure (IOP) lowering effects in rabbits with ocular hypertension (OHT). Methods: The IOP lowering effect of a single drop of OB extract (OBE) was evaluated in oculonormotensive rabbits using three concentrations (0.25, 0.5 and 1% w/v). The concentration showing maximum IOP reduction was further evaluated in rabbits with water-loading and steroid-induced OHT. Results: IOP lowering effect of OBE 0.5% in oculonormotensive rabbit eyes was significantly greater compared to OBE 0.25% (p<0.05) but was comparable (p>0.05) to OBE 1%. Therefore, 0.5% concentration was selected for further evaluation. Pretreatment with OBE (0.5%) caused significantly lower increase in IOP after water loading amounting to 23.39% above baseline as compared to 54.00% in control eye, 15 minutes post water loading. At 60 minutes, post water loading, mean IOP rise was 95.12% and 63.58% in control and test eyes, respectively. Significant difference between the mean IOP of two eyes persisted during the 2nd hr. In rabbits with steroid induced OHT, OBE 0.5% produced a mean IOP reduction of 24.73% at the end of first hr and the mean peak IOP reduction of 31.63% was observed at the end of 2 hr. A significant difference between the IOP of test and control eyes persisted from 1 to 6 hr. Conclusions: Ocimum basilicum seed extract showed significant IOP lowering effect in rabbits with water loading and steroid induced OHT, however, its utility as an effective antiglaucoma medication needs further investigations.