DISCOVERY OF PYRAZOLOPYRIDINE DERIVATIVES DUALLY TARGETING INFLAMMATION AND PROLIFERATION IN COLORECTAL CANCER CELL LINES: IN-SILICO DRUG DESIGN APPROACH

Abstract

Elimination of inflammation represents a promising strategy for cancer prevention and treatment since cancer and inflammation are related. The combined use of anti-inflammatory agents and cancer therapy is a focal point. In this frame, pyrazolopyridine derivatives DZ-BAU2021-6 and DZ-BAU2021-14, developed in BAU Labs, having promising anti-proliferative activity on colon cancer cells HCT-116 and HT-29 with notable IC50 values and remarkable CDK2 inhibitory effect, were in-silico tested. As an approach to dual anti-inflammatory anticancer potential, their binding modes and energies on the active site of crystalline structure of CDK2 and COX2, (1HCK and 3LN1), respectively were explored. Their physicochemical and pharmacokinetic properties as well as their "drug-likeness" were studied. Computational results declared that DZ-BAU2021-6 and DZ-BAU2021-14 exhibited high binding affinities to CDK2 and COX2 receptors. DZ-BAU2021-14 exhibited lower levels of estimated binding energies with COX2 receptor compared to Celecoxib. It demonstrated high GI absorption, low interference with P-glycoprotein and cytochrome P450 isoforms.