Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL.

This work reviews the use of terpenes available from renewable resources in the fine chemicals industry. Different products and processes are discussed. Transformations of terpenes involving isomerization, hydration, condensation, hydroformylation, hydrogenation, cyclization, oxidation, rearrangement, and ring contraction/enlargement are routes to produce a variety of compounds of interest to the pharmaceutical, agrochemical, and flavors and fragrances industries.

Catalytic Conversion of Terpenes into Fine Chemicals

Advances in Induction and Microwave Heating of Mineral and Organic Materials

Citronellal as key compound in organic synthesis

The main purpose of this review is to summarize recent chemical syntheses and structural modifications of 4-hydroxycoumarin and its derivatives, of interest due to their characteristic conjugated molecular architecture and biological activities.

https://www.mdpi.com/1420-3049/14/11/4790/pdf

Synthetic Approaches and Biological Activities of 4-Hydroxycoumarin Derivatives

High chemoselectivity in microwave accelerated intramolecular domino Knoevenagel hetero Diels–Alder reactions—an efficient synthesis of pyrano[3-2c]coumarin frameworks

S. Manikandan

Papers

High chemoselectivity in microwave accelerated intramolecular domino Knoevenagel hetero Diels–Alder reactions—an efficient synthesis of pyrano[3-2c]coumarin frameworks

Competition between two intramolecular domino Knoevenagel hetero Diels-Alder reactions: a new entry into novel pyranoquinolinone derivatives

Synthesis of Spiroisoxazoline[5.31]-chroman-41-one.

A formal [3 + 2] cycloaddition strategy for the synthesis of unique class of dispiroheterocycles

An Easy Access to Spiroisoxazoline [5,31] Flavan-41-one Through 1,3-Dipolar Cycloaddition Reaction of Nitrile Oxide to Unusual Dipolarophiles