Current Topics in Medicinal Chemistry - Volume 17, Issue 22, 2017

For successful drug discovery it is important to understand the fundamentals of the underlying causes and consequences of the diseases for which the drug is being developed. One such physiological process in eukaryotic cells is protein phosphorylation, which is the main post-translational modification of proteins responsible for the onset or progression of Alzheimer's disease, diabetes and various cancers. Protein phosphor Read More

Role of kinase inhibitors in various diseases is well established and discovery of imatinib opens up new paradigms in kinase inhibition. Furthermore, presence of heterocyclic moiety in a kinase inhibitor seems to be essential now. However, the potential of a single heterocyclic moiety was discussed in variety of reviews but a focus review considering the potential of different heterocyclic moieties is unavailable. Based on thi Read More

In recent years, several scientific investigations have reported the therapeutic implications of superoxide dismutase (SOD) against oxidative stress and -induced pathology in clinical and preclinical trials. Indeed, various kinase, molecular signaling and physiological process has altered by reactive oxygen species. In spite of the abundant available literature reports, patents, clinical trials and commercialized products, the therapeuti Read More

Mutations in the kinase domain encoding region of EGFR gene causes drug resistance to EGFR kinase inhibitors such as erlotinib and gefitinib. This problem can be addressed by a new lead compound effective against all mutants of EGFR. To predict positions of residues possessing the potential to render EGFR drug resistant upon mutation, residual positions known to interact with Erlotinib and Gefitinib were assessed using five p Read More

Microtubules form crucial dynamic structural cellular components of the cell and are composed of the alpha beta tubulin heterodimers. Microtubules are involved in a wide variety of functions in the cell such as attribution to cell shape, motility, intracellular trafficking and mitotic spindle formation. Owing to these reasons, tubulin and microtubules have gained significant interest as important targets for cancer the Read More

In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard to βIII, which is commonly over-expressed in cancer. Computational prediction, protein-based and cell-based assays Read More

Microtubule-targeted drugs (MTDs) have been on the forefront of breast cancer chemotherapy. Classic MTDs, such as paclitaxel and their semisynthetic derivatives, have achieved considerable success in the clinical management of breast neoplasms. In order to improve the specificity and to reduce undesirable, dose-limiting toxicities of these drugs, a plethora of novel compounds are being synthesized and investigated Read More

We have recently reported the synthesis and antiproliferative potential of a series of biaryl type α-noscapine congeners. Among them, 9-(3-pyridyl) noscapine 3f (9-PyNos, henceforth), which was synthesized by adding pyridine unit to the tetrahydroisoquinoline part of natural α-noscapine core, was found to be the most effective one to inhibit proliferation of a variety of cancer cell lines. However, details of its interactions with its Read More