Overcoming vincristine resistance in cancer: Computational design and discovery of piperine-inspired P-glycoprotein inhibitors.

P-glycoprotein (P-gp)/MDR-1 plays a major role in the development of multidrug resistance (MDR) by pumping the chemotherapeutic drugs out of the cancer cells and reducing their efficacy. A number of P-gp inhibitors were reported to reverse the MDR when co-administered with chemotherapeutic drugs. Unfortunately, none has approved for clinical use due to toxicity issues.

Design of a potent anticancer lead inspired by natural products from traditional Indian medicine.

Among the plant constituents of Walp., acteoside, martinoside, and osmanthuside β6 interact with ROCK, a drug target for cancer. In this study, aglycone fragments of these plant constituents (caffeic acid, ferulic acid, and -coumaric acid) along with the homopiperazine ring of fasudil (standard ROCK inhibitor) were used to design hybrid molecules.

Insights for the design of protein lysine methyltransferase G9a inhibitors.

The epigenetic control of gene expression could be affected by addition and/or removal of post-translational modifications such as phosphorylation, acetylation and methylation of histone proteins, as well as methylation of DNA (5-methylation on cytosines). Misregulation of these modifications is associated with altered gene expression, resulting in various disease conditions. G9a belongs to the protein lysine methyltransferases that specifically methylates the K9 residue of histone H3, leading to suppression of several tumor suppressor genes.

In Silico and In Vitro Investigation of the Piperine's Male Contraceptive Effect: Docking and Molecular Dynamics Simulation Studies in Androgen-Binding Protein and Androgen Receptor.

Understanding the molecular mechanism of action of traditional medicines is an important step towards developing marketable drugs from them. Piperine, an active constituent present in the Piper species, is used extensively in Ayurvedic medicines (practiced on the Indian subcontinent). Among others, piperine is known to possess a male contraceptive effect; however, the molecular mechanism of action for this effect is not very clear.