Abstract
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.
Highlights
Chemotherapeutics are the most important tool in the fight against cancer
We have developed a new and facile method for the synthesis of N-acylated sulfonamides using
The newly synthesized N-acylsulfonamides were tested for their in vitro cytotoxic activity against the MCF-7, HCT-116 and HeLa cell lines
Summary
Chemotherapeutics are the most important tool in the fight against cancer. For decades scientists have discovered many anticancer drugs by designing low-molecular weight compounds with the ability to bind to a preselected protein target or by screening small molecules for their ability to modulate a biological pathway in cells or organisms, or without regard for any particular protein target [1,2]. A promising solution that is a focus of contemporary medicinal chemistry is the development of potent and selective anticancer drugs. Many of these new agents are being tested in combination with therapies currently used to treat specific cancers and usually include cytotoxic drugs. Our systematic studies on aryl- and heteroarylsulfonamides have resulted in promising anticancer agents [19,20,21,22,23,24], among which we have reported some N-acylsulfonamides (I, Figure 2) with antiproliferative activity against a broad spectrum of cancer cell lines [23]. One of the parameters characterizing the pharmacokinetic properties of a molecule, was performed using pooled human liver microsomes and NADPH
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
