Effect of Anti-Retroviral Drug Impurity/Related Substances on the CCR5 and/or CXCR4 Receptors Binding Sites to Revise Resistance Mechanisms in the Clinical Implications Using Molecular Docking Studies.

BACKGROUND: CCR5 and/or CXCR4 receptors on CD4+ T cell membranes are the active sites for HIV to bind. The different classes of drugs have a unique mechanism of action to cease the virus, but we are concentrating in the first-class i.e. NNRTI that destroys the virus while it binds to the cell surface gp120 protein. The drugs are having several impurities that can be genotoxic and few are reported in the monographs. OBJECTIVE: This study proposes the affinity of the impurities to the active site through molecular docking to a receptor (PDB ID 4MBS) from the library of analogs available for antiretroviral drugs. As these drugs are taken for the long term, this study will give a prominent idea for testing the impurities and their genotoxicity. METHODS: We have done molecular docking of 37 impurities and drugs with the GLIDE module of schrodinger software for their binding affinities. In this study, receptor CCR5 and/or CXCR4 is selected containing glycoprotein that mediates virus binding to CD4+ T cell. RESULTS: Didanosine E and Zidovudine D shows maximum and minimum score respectively. The selected impurities were interfering with the active binding site that may lead to any ADR or reduce the effect of API. CONCLUSION: Conclusively, a significant role is played by Protein-Ligand interaction in structuralbased designing. Summarizing that there might be a genotoxicity effect due to competition between API and the impurities. The molecular docking was used to study the binding mechanism and to establish the docking score along with the activity. The outcome of the study can be used to design and development of novel compounds having genotoxicity.

Sonic Hedgehog gene as a potential target for the early prophylactic detection of cancer.

In the search for newer and advanced methods for the detection of cancer, quicker and non-invasive techniques are imperative. One such potential approach for detection is the detection of oncogenes in the suspected tumour tissues. This search has led to the identification of the oncogene SHh, which is a key influencer in the tumourigenic pathways. Therefore, a cancer detection method, which would target the identification of the oncogene SHh would therefore be a step forward in the advancement of cancer research.

A Sensitive RP-HPLC Method for Simultaneous Estimation of Diethylcarbamazine and Levocetirizine in Tablet Formulation.

A simple, sensitive and reproducible method was developed and validated for the simultaneous estimation of diethylcarbamazine and levocetirizine in its tablet formulation by reverse phase high performance liquid chromatography using Waters1515 HPLC with UV detector at the λ(max) of 224 nm, using Princeton Sphere-100 C(18) (250×4.6 mm. 5 µ) column. The mobile phase used was 20mM potassium dihydrogen orthophosphate buffer (pH: 3.2):acetonitrile (50:50 v/v) with isocratic flow (flow rate 1 ml/min) and the pH was adjusted with orthophosphoric acid. Losartan potassium was used as an internal standard. The compounds diethylcarbamazine, levocetirizine and losartan potassium were eluted at 2.12, 4.27 and 5.96 min, respectively. The peaks were eluted with better resolution. The method was accurate with assay values of 96.32 and 93.04% w/w, precise (%RSD) with intra-day 1.72 and 1.89 and inter-day 1.85 and 1.92, recoveries 102.86 and 101.1% w/w, which are very sensitive with limit of detections (LOD)'s 75, 50 ng/ml and limit of quantification (LOQ)'s 100, 75 ng/ml and linear with R(2) values 0.994 in the range of 5 to 30 µg/ml 0.1 to 1 µg/ml for diethylcarbamazine and levocetirizine, respectively. Hence this method can be applied for quantification of different formulations containing diethylcarbamazine and levocetirizine simultaneously.