Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides.
A series of novel N-acyl-4-chloro-5-methyl-2-(R¹-methylthio)benzenesulfonamides 18-47 have been synthesized by the reaction of N-[4-chloro-5-methyl-2-(R¹-methylthio) benzenesulfonyl]cyanamide potassium salts with appropriate carboxylic acids. Some of them showed anticancer activity toward the human cancer cell lines MCF-7, HCT-116 and HeLa, with the growth percentages (GPs) in the range from 7% to 46%. Quantitative structure-activity relationship (QSAR) studies on the cytotoxic activity of N-acylsulfonamides toward MCF-7, HCT-116 and HeLa were performed by using topological, ring and charge descriptors based on the stepwise multiple linear regression technique (MLR). The QSAR studies revealed three predictive and statistically significant models for the investigated compounds. The results obtained with these models indicated that the anticancer activity of N-acylsulfonamides depends on topological distances, number of ring system, maximum positive charge and number of atom-centered fragments. The metabolic stability of the selected compounds had been evaluated on pooled human liver microsomes and NADPH, both R¹ and R² substituents of the N-acylsulfonamides simultaneously affected them.
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. zolnowska@gumed.edu.pl.
Beata
B
Żołnowska
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. jaroslaw@gumed.edu.pl.
Jarosław
J
Sławiński
Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. mariusz.belka@gumed.edu.pl.
Mariusz
M
Belka
Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. tbaczek@gumed.edu.pl.
Tomasz
T
Bączek
Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, ul. Kładki 24, 80-822 Gdańsk, Poland. kawiak@biotech.ug.pl.|Department of Human Physiology, Medical University of Gdańsk, ul. Tuwima 15, 80-210 Gdańsk, Poland. kawiak@biotech.ug.pl.
Anna
A
Kawiak
Department of Inorganic Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland. jarekch@pg.gda.pl.
Jarosław
J
Chojnacki
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. anetapogorzelska@gumed.edu.pl.
Aneta
A
Pogorzelska
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland. k.szafranski@gumed.edu.pl.
Krzysztof
K
Szafrański
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008862:Microsomes, Liver / Q000378:metabolism; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D013449:Sulfonamides
QSAR; anticancer; metabolic stability; sulfonamide; synthesis