title: Analogue based drug design, synthesis, molecular docking and anticancer evaluation of novel chromene sulfonamide hybrids as aromatase inhibitors and apoptosis enhancers.
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.
authors: 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.
authors: Mostafa M
authors: MM
authors: Ghorab
authors: Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, 11451 Riyadh, Saudi Arabia.
authors: Mansour S
authors: MS
authors: Alsaid
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, 11566 Cairo, Egypt.
authors: Ghada H
authors: GH
authors: Al-Ansary
authors: Department of Pharmacology, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
authors: Ghada A
authors: GA
authors: Abdel-Latif
authors: 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.
authors: Dalal A
authors: DA
authors: Abou El Ella
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001141:Aromatase / Q000737:chemistry / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D059748:Proteolysis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D001578:Benzopyrans; D013449:Sulfonamides; D001141:Aromatase
keywords: Apoptosis; Aromatase inhibitors; Breast cancer; Chromene; Sulfonamides