Tapan K. Mukherjee

Intercellular adhesion molecule‐1 as a drug target in asthma and rhinitis

Intercellular adhesion molecule‐1 (ICAM‐1) is a transmembrane glycoprotein receptor of the immunoglobulin superfamily. Endothelial cells, epithelial cells, leukocytes and neutrophils are the major cells expressing ICAM‐1. Ligands of ICAM‐1 are macrophage adhesion ligand‐1, leukocyte function‐associated antigen‐1 and fibrinogen (extracellular matrix protein). In normal physiological conditions, engagement of ICAM‐1 receptor with immunological cells surface ligands assists in homing and trafficking of inflammatory cells to distant tissues. ICAM‐1 has also long been known to mediate cell‐to‐cell interaction during antigen presentation and outside‐in cell signalling pathways. ICAM‐1‐mediated elevated inflammation is implicated in asthma. On respiratory epithelial cells surface, ICAM‐1 acts as natural binding site for human rhinovirus (HRV), a common cold virus that ultimately causes exacerbation of asthma. This review presents the findings on the role of ICAM‐1 in the complication of asthma and in particular asthma exacerbation by HRV.

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

Abstract The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.

Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends and advancements

&NA; For several decades, bioactive phytochemicals have been appreciated to prevent and cure various lethal diseases. Many studies have proven the ability of dietary phytochemicals to avoid and retard tumor initiation and progression. Among the pharmacologically active moieties, terpenoids are considered one of the most important classes. Carnosol, is also a kind of diterpenoid, which known to possess a range of therapeutic effects such as anti‐cancer, anti‐inflammatory, and anti‐oxidant activities. All these effects are mediated via modulating different signaling cascades, including apoptosis regulating molecules (Bax/Bcl2), prosurvival‐proproliferative molecules (Akt/mTOR, MAPK), transcription factors like NF‐kappaB, STAT3‐6, and steroid receptors, such as androgen and estrogen receptors. The present review highlights the recent trends and advancements have been done in the field of research by using carnosol. Graphical abstract Figure. No caption available.

Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each others independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D (1)H and (13)C NMR spectroscopy. Binding leads to attenuation of E2s hydroxyl (1)H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each others levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas.

Molecular dynamics simulation as a tool for assessment of drug binding property of human serum albumin

Human serum albumin (HSA) is a major plasma protein and binding of drugs with this plasma protein has a great importance. It possess esterase activity which can cleave the drugs containing ester bond and thus, can regulate the effect of drugs. Till date no systematic study has been done to analyse binding of such drugs and to compare the results with the drugs which do not have ester bond. Therefore, in the present study two different categories—ester and non-ester drugs have been considered to analyse their interaction with HSA at two principle drug binding sites using molecular modelling tools. It is observed that the drugs irrespective of ester or non-ester nature prefer either Sudlow site I or II by hydrogen bond and hydrophobic interactions. The information obtained from the study can assist to study pharmacokinetics of the drugs and that in turn will help in noval drug discoveries.

Designing of a penta-peptide against drug resistant E. coli

Drug resistant pathogens are vibrant global problem. Penicillin binding protein 5 (PBP5) plays important role in bacterial cell wall biosynthesis. Mutation in PBP5 is a well-known mechanism for development of drug resistant strain of bacteria. In this context we have designed a peptide that fits better at the ligand-binding site of mutant PBP5 compared to wild type PBP5. It is expected that the designed peptide will halt the growth of drug resistant pathogen harboring mutant variety of PBP5. We have recommended experimental validation of the above concept.

Immunogenic decapeptide in melanoma immunotherapy

Melanoma is a cancer associated with melanocytes of epidermis. There has been a consistent increase in the number of melanoma patients because of the depletion of the ozone layer which makes it of paramount importance to explore the immunogenic potential of various peptides in melanoma therapy. In the current study, a mutated decapeptide (ELAGIGILTV) epitope ID 12941 was taken from the melanoma antigen recognized by T-cells. This epitope displayed relatively better affinity for histocompatibility leukocyte antigen influencing the proliferation of cytotoxic T-cells. Immunogenicity of the oligopeptide can be further intensified by its simultaneous binding to the programmed death receptor of the T lymphocytes. We have used the molecular dynamics (MD) simulation approach to reveal the dynamics of the decapeptide and its consequences to immunogenic effects. The dynamics have ensembled various conformations of the peptide which have been clustered in their representative conformers. During the dynamics, the peptide was found to fold to its conformation with a minimum free energy. Moreover, multiple analysis of the MD trajectory has provided many physiochemical features involved in the biological activity to improve the immunogenicity of this antigenic peptide. The manuscript concludes by proposing this decapeptide as a potential vaccine for the melanoma cancer.