Synthesis, carbonic anhydrase inhibition and cytotoxic activity of novel chromone-based sulfonamide derivatives.
Four series of sulfonamides incorporating chromone moieties were synthesized and assessed for their cytotoxic activity against MCF-7 and A-549 cell lines, considering the fact that some of these tumors overexpress isoforms of carbonic anhydrase (CA, EC 4.2.1.1) which is inhibited by sulfonamides. Most new sulfonamides showed weak inhibitory activity against the offtarget, cytosolic isoforms hCA I, II but effectively inhibited the tumor-associated hCA IX and XII. The most active compounds featured a primary SO2NH2 group and were active in the low micromolar range against MCF-7 and A-549 cell lines. Compound 4a showed IC50 of 0.72 and 0.50 μM against MCF-7 and A-549 cell lines, respectively, and was further evaluated for its proapoptotic activity which proved enhanced in both tumor types.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt. Electronic address: fadi_mae@hotmail.com.
Fadi M
FM
Awadallah
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
Tamer A
TA
El-Waei
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
Mona M
MM
Hanna
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
Safinaz E
SE
Abbas
University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy.
Mariangela
M
Ceruso
University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy; Yildirim Beyazit University Faculty of Medicine, Department of Medical Biology, Cinnah Campus, Ankara, Turkey.
Beyza Ecem
BE
Oz
University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy; Yildirim Beyazit University Faculty of Medicine, Department of Medical Biology, Cinnah Campus, Ankara, Turkey.
Ozen Ozensoy
OO
Guler
University of Florence, Neurofarba Department, Via Ugo Schiff 6, Polo Scientifico, 50019, Sesto Fiorentino, Firenze, Italy. Electronic address: claudiu.supuran@unifi.it.
Claudiu T
CT
Supuran
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D002867:Chromones; D013449:Sulfonamides; D002256:Carbonic Anhydrases
Breast cancer; Carbonic anhydrase; Chromone; Lung cancer; Sulfonamide