Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study

Molecules

Aneta Pogorzelska¹  Jarosᐪw Sᐪwiński¹  Kamil Bro៎wicz¹  Szymon Ulenberg³  Tomasz Bၜzek³  Jean Jacques Vanden Eynde² 

[1] Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland;;Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, PolandDepartment of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland;

关键词: 1;    4;    2-benzodithiazines;    sulfonamide;    QSAR;    anticancer activity;   

DOI  :  10.3390/molecules201219821

来源: mdpi

【 摘 要 】

A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5a–j have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468) cancer (10% and 47% cancer cell death, respectively) as well as a good selectivity toward prostate (DU-145), colon (SW-620) and renal (TK-10) cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5a–j QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively) and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models) descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained.

【 授权许可】

CC BY   
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