Design, Facile Synthesis, Characterization and Computational Evaluation of Novel Isobutylchalcones as Cytotoxic Agents: Part-A

Afzal Basha SHAIK*°, Y. Rajendra PRASAD*, Shaik SHAHANAAZ**

*A.U College of Pharmaceutical Sciences, Andhra University, 53000, Andhra Pradesh, India.
**Victoria College of Pharmacy, 522001, Andhra Pradesh, India.

Corresponding Author:
E-mail: bashafoye@gmail.com

Summary

A series of novel isobutylchalcones (A1-A20) were prepared, evaluated for their cytotoxic activity and characterized by FTIR, 1H NMR, 13C NMR, and elemental analysis data. The logic behind the design was to synthesize and compare chalcones containing electron releasing lipophilic isobutyl substituent on aromatic ring A and the B ring with aromatic ring containing a range of electron releasing and electron withdrawing groups as well as heteroaromatic rings for their cytotoxic activity. The compounds were tested against HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines using methotrexate (IC50 12 ± 1 (HT-29), 9 ±1 (MCF- 7) 5 ± 1 (DU-145)) as reference standard. Compound A6 having 2,4-difluorophenyl moiety was the most potent of the series against all the three cell lines and notably A6 was mainly effective against DU-145 cell lines with an IC50 value of 18 μg/mL. The critical structural features required for the activity against all the cell lines were identified through pharmacophore model using PHASETM which has recognised a 5 point AHHRR model and is consistent with the cytotoxic activity of the tested compounds.

Key Words :
Chalcone, Cytotoxic activity, Pharmacophore model, PHASETM, AHHRR model