Anticancer and radio-sensitizing evaluation of some new thiazolopyrane and thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety

Recently, it has been reported that compounds bearing a sulfonamide moiety posses many types of biological activities, including anticancer activity. There are a variety of mechanisms for their anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work reports the synthesis of some new thiazolo[4,5-b]pyrane, thiazolo[4,5-b]pyrano[2,3-d]pyrimidine derivatives bearing a sulfonamide moiety. The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 5, 6, 10 and 12 (IC50 values 39.4 μM, 41.6 μM, 35.72 μM and 34.64 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC50 = 71.8 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ–radiation.

The present work reports the synthesis of fourteen novel thiazolopyrane and thiazolpyranopyrimidine derivatives bearing a sulfonamide moiety (5–18), and the evaluation of their in vitro anticancer activity alone or in combination with γ-irradiation.Figure optionsDownload as PowerPoint slideHighlights
► We synthesized fourteen novel thiazolopyrane and thiazolpyranopyrimidine derivatives bearing a sulfonamide moiety.
► All the newly synthesized compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7).
► The most four active compounds were selected to be evaluated again as cytotoxic agents against MCF7 cells in combination with γ-radiation, and showed radio-sensitizing activities.