Synthesis, Molecular Structure, Metabolic Stability and QSAR Studies of a Novel Series of Anticancer N-Acylbenzenesulfonamides

Abstract

A series of novel N-acyl-4-chloro-5-methyl-2-(R 1-methylthio)benzenesulfonamides 18-47 have been synthesized by the reaction of N- [4-chloro-5-methyl-2-(R 1 -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 OPEN ACCESSMolecules 2015, 20 19102 number of atom-centered fragments. The metabolic stability of the selected compounds had been evaluated on pooled human liver microsomes and NADPH, both R 1 and R 2 substituents of the N-acylsulfonamides simultaneously affected them.

N-(2-Arylmethylthio-4-Chloro-5-Methylbenzenesulfonyl)amide Derivatives as Potential Antimicrobial Agents—Synthesis and Biological Studies

“…The starting N-(benzenesulfonyl)cyanamide potassium salts 3-7 were prepared by reaction of 3-amino-1,1-dioxo-1,4,2-benzodithiazine (1) with anhydrous K 2 CO 3 and alkylating agents according to reported procedures [14,15]. For the synthesis of novel N-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)amide derivatives 8-12, the convenient acylation of sulfonamides was used [16]. The N-(2-arylmethylthio-4-chloro-5methylbenzenesulfonyl)-3-cyclohexylpropanamides 8-12 were obtained by heating monopotassium salts 3-7 with cyclohexylpropanoic acid at 115 • C for 1-2 h, with 70-85% yield (Scheme 1).…”

“…Melting point and spectroscopic analysis were in accordance with the previously described in [16]. (16) Starting with 6 (0.309 g), the title compound (16) was obtained after previous crystallization from ethanol (0.196 g, 55%). Melting point and spectroscopic analysis were in accordance with the previously described in [16].…”

“…(16) Starting with 6 (0.309 g), the title compound (16) was obtained after previous crystallization from ethanol (0.196 g, 55%). Melting point and spectroscopic analysis were in accordance with the previously described in [16]. Starting with 7 (0.309 g), the title compound (17) was obtained after previous purification on silica gel using AcOEt/n-hexane (v/v = 1:3) as an eluent (0.242 g, 68%): m.p.…”

Synthesis of 2-alkylthio-N-(quinazolin-2-yl)benzenesulfonamide derivatives: anticancer activity, QSAR studies, and metabolic stability

“…Among them, one of the most important and the largest is a group of N -arylsulfonamides in which the aryl/heteroaryl substituent is connected directly to the sulfonamide nitrogen atom [ 4 – 8 ]. Our team, carrying research on a multidirectional activity of various 2-mercaptobenzenosulfonamide (MBSA) derivatives, have found high anticancer potential in this class of compounds [ 9 – 12 ]. Thus, aiming to obtain a synergistic effect by combining MBSA scaffold and an aryl substituent with proven biological activity, we decided to synthesize and examined the anti-tumor properties of the 4-chloro-2-thio- N -(quinazolin-2-yl)benzenesulfonamides 9 – 24 (Scheme 1 ) in which the quinazoline ring is attached to the 2-mercaptobenzenesulfonamide core.…”

An Optimized Synthesis, Molecular Structure and Characterization of Benzylic Derivatives of 1,2,4-Triazin-3,5(2H,4H)-dione

“…They have been reported to possess a broad spectrum of biological properties and are used in medicine. In the last decade numerous compounds with the 1,2,4-triazine moiety have been synthesized, along with numerous biological tests, thus revealing their varied bioactivity, such as benzodiazepine receptor inhibition [ 2 ], antimicrobial [ 3 , 4 ], anxiolytic [ 5 , 6 ], neuroprotective [ 7 ], antifungals [ 8 ], anti-inflammatory [ 6 , 9 ], antiparasitic [ 10 ], antiparkinson [ 11 ], and anticancer [ 12 , 13 , 14 , 15 ] activities.…”