In vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety

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• 作者：Mostafa M. Ghorab ; Fatma A. Ragab ; Helmy I. Heiba ; Reem K. Arafa ; Ebaa M. El-Hossary
• 关键词：Quinoline ; Pyrimido[4 ; 5-b]quinoline ; Sulfonamide ; Carbonic anhydrase II ; Anticancer ; γ ; -Radiation
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：45
• 期：9
• 页码：3677-3684
• 全文大小：392 K

文摘

Sulfonamide bearing compounds posses many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There are a variety of mechanisms for the anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work reports the synthesis of twenty novel quinoline and pyrimido[4,5-b]quinoline derivatives bearing a sulfonamide moiety. The new synthesized compounds were designed in compliance with the general pharmacophoric requirements for CA inhibiting anticancer drugs, as this may play a role in their anticancer activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 6, 9 and 18 showed IC₅₀ values (72.9 μM, 72.1 μM and 71.9 μM, respectively) comparable to that of the reference drug doxorubicin (IC₅₀ = 71.8 μM). On the other hand, compound 8 exhibited better activity than doxorubicin with an IC₅₀ value of 64.5 μM. Additionally, the most potent compounds 8 and 18 were evaluated for their ability to enhance the cell killing effect of γ-radiation.