2. Academic Validation
  3. Analogue based drug design, synthesis, molecular docking and anticancer evaluation of novel chromene sulfonamide hybrids as aromatase inhibitors and apoptosis enhancers

Analogue based drug design, synthesis, molecular docking and anticancer evaluation of novel chromene sulfonamide hybrids as aromatase inhibitors and apoptosis enhancers

  • Eur J Med Chem. 2016 Nov 29:124:946-958. doi: 10.1016/j.ejmech.2016.10.020.
Mostafa M Ghorab 1,  Mansour S Alsaid 2,  Ghada H Al-Ansary 3,  Ghada A Abdel-Latif 4,  Dalal A Abou El Ella 5
Affiliations

Affiliations

  • 1 Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, 11451 Riyadh, Saudi Arabia; Department of Drug Radiation Research, National Center for Radiation Research and Technology, Nasr City, 113701 Cairo, Egypt. Electronic address: mmsghorab@yahoo.com.
  • 2 Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, 11451 Riyadh, Saudi Arabia.
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.
  • 4 Department of Pharmacology, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, 62511 Beni Suef, Egypt.
PMID: 27770735 DOI: 10.1016/j.ejmech.2016.10.020
Abstract

Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro Anticancer activity against breast Cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the Anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested. Most of the selected compounds showed significant inhibitory effect on the aromatase activity, with compound 18 showing IC50 = 4.66 μM. Furthermore, Apoptosis studies were conducted on two of the most potent compounds (8 & 16) to estimate the proapoptotic potential of our compounds. Both induced the levels of active Caspase 3, Caspase 8 and Caspase 9. Moreover, they surprisingly boosted the Bax/Bcl2 ratio 5936 & 33,000 folds, respectively compared to the control. Moreover, they showed mild cytotoxic effect (IC50 = 183.8 μM & 172.04 μM, respectively) in normal breast cells 184A1. Finally, a molecular docking study was performed to investigate the probable interaction with the aromatase Enzyme.

Keywords

Apoptosis; Aromatase inhibitors; Breast cancer; Chromene; Sulfonamides.

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