Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of -(aryl/heteroaryl)-4-(1-pyrrol-1-yl)Benzenesulfonamide Derivatives.

A series of -(aryl/heteroaryl)-4-(1-pyrrol-1-yl)benzenesulfonamides were synthesized from 4-amino--(aryl/heteroaryl)benzenesulfonamides and 2,5-dimethoxytetrahydrofuran. All the synthesized compounds were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. Compound , bearing 8-quinolinyl moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC values of 3, 5, and 7 µM, respectively.

Synthesis and QSAR study of novel 6-chloro-3-(2-Arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives with anticancer activity.

A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed.

Synthesis of a new series of N⁴-substituted 4-(2-aminoethyl)benzenesulfonamides and their inhibitory effect on human carbonic anhydrase cytosolic isozymes I and II and transmembrane tumor-associated isozymes IX and XII.

A series of novel N(4)-substituted 4-(2-aminoethyl)benzenesulfonamides 5-17 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Synthesis of a new series of biologically interesting 6'-chloro-1',1'-dioxospiro[4-benzo[][1,3,7]oxadiazocine-4,3'(2')-[1,4,2]benzodithiazine]-2,6(1,5)dione derivatives.

Abstract: A series of 6'-chloro-1',1'-dioxospiro[4-benzo[][1,3,7]oxadiazocine-4,3'(2')-[1,4,2]benzodithiazine]-2,6(1,5)dione derivatives have been synthesized from isatoic anhydride and 3-(R-amino)-1,4,2-benzodithiazine 1,1-dioxides. Some synthetic limitations are discussed on the basis of quantum chemical calculations performed by use of the Hartree-Fock method.

Carbonic anhydrase inhibitors. Regioselective synthesis of novel series 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII.

A series of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides 4-6, 9-17 and 21-31 have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA.EC 4.2.

Carbonic anhydrase inhibitors. Synthesis, molecular structures, and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with novel 3-pyridinesulfonamide derivatives.

A series of novel 3-pyridinesulfonamide derivatives (2-5, 9-11 and 13-15) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors. Regioselective synthesis of novel 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamides and their inhibition of the human cytosolic isozymes I and II and transmembrane cancer-associated isozymes IX and XII.

A series of 1-substituted 1,4-dihydro-4-oxo-3-pyridinesulfonamide (2-16) have been synthesized and investigated as inhibitors of four isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors: synthesis and inhibition of the human cytosolic isozymes I and II and transmembrane isozymes IX, XII (cancer-associated) and XIV with 4-substituted 3-pyridinesulfonamides.

A series of novel 4-substituted-3-pyridinesulfonamides (2-27 and 31-33) have been synthesized and investigated as inhibitors of five isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Synthesis and anti-HIV-1 integrase activities of 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines.

A series of novel 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines 15-28 as potential HIV-1 integrase (IN) inhibitors have been synthesized by the reduction of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines 1-14 with benzenesulfonyl hydrazide. All the compounds 15-28 inhibited IN mediated strand transfer reaction with IC(50) values ranging from 3 to 30 microM. The 3-(4-bromobenzoyl)-6-chloro-7-methyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazine 17 with the IC(50) values of 4+/-1 and 3+/-1 microM for 3'-processing and strand transfer, respectively, was the most potent.

Carbonic anhydrase inhibitors: inhibition of human cytosolic isozymes I and II and tumor-associated isozymes IX and XII with S-substituted 4-chloro-2-mercapto-5-methyl-benzenesulfonamides.

A series of S-substituted 4-chloro-2-mercapto-5-methyl-benzenesulfonamides has been investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Synthesis, anti-HIV-1 integrase, and cytotoxic activities of 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives.

Several 4-chloro-N-(4-oxopyrimidin-2-yl)-2-mercaptobenzenesulfonamide derivatives 13-28 and 35-44 have been synthesized and tested as potential HIV-1 integrase (IN) inhibitors. Compounds 15-17, 19, 21-28, 36 and 41 inhibited IN with IC(50) values in the range of 3.3-63.

Synthesis of novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)-guanidine derivatives as potential antitumor agents.

Novel 3-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives have been synthesized as potential anticancer agents. The in vitro antitumor activity of these compounds has been evaluated in the US National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed. The prominent compound was 1-allyl-2-[4-chloro-5-(4-chlorophenylcarbamoyl)-2-methylthiobenzenesulfonyl]-3-(5-nitrofurfurylideneamino)guanidine (8) with remarkable activity against 21 human tumor cell lines representing leukemia, lung, colon, melanoma, ovarian, renal, prostate and breast (GI(50)=0.

Synthesis, structural characterization, and in vitro antitumor activity of novel N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamides.

A new series of N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamides 23-48 have been synthesized as potential anticancer agents. All compounds were screened for their cytotoxic activity against six human tumor cell lines. The selected compounds 23-27, 30, 31, 33, 35, 38, 42, 45, and 46 were further tested at the US National Cancer Institute for their in vitro activities against a panel of 53-59 human tumor cell lines.

Carbonic anhydrase inhibitors. Selective inhibition of human tumor-associated isozymes IX and XII and cytosolic isozymes I and II with some substituted-2-mercapto-benzenesulfonamides.

A series of 2-mercapto-substituted-benzenesulfonamides has been prepared by a unique two-step procedure starting from the corresponding 2-chloro-substituted benzenesulfonamides. Compounds bearing an unsubstituted mercapto group and the corresponding S-benzoyl derivatives were investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.

Synthesis and anti-HIV-1 activity of a novel series of 1,4,2-benzodithiazine-dioxides.

Previously, we discovered a series of novel benzodithiazines-dioxides with both antiviral and anticancer activities. In order to design compounds with distinct antiviral properties, we prepared new compounds with modifications on the imidazole and pyrimidine rings. Herein, we present the synthesis and antiviral activity of 8-chloro-2,3-dihydroimidazo[1,2-b][1,4,2]benzodithiazine 5,5-dioxides (22, 23, 30, and 31) and 9-chloro-2,3,4-trihydropyrimido[1,2-b][1,4,2]benzodithiazine 6,6-dioxides (14, 24, 25, and 27).

Carbonic anhydrase inhibitors. Inhibition of the cytosolic human isozymes I and II, and the transmembrane, tumor-associated isozymes IX and XII with substituted aromatic sulfonamides activatable in hypoxic tumors.

Some 2-mercapto-substituted-benzenesulfonamides and their disulfides/sulfones were prepared and investigated as inhibitors of four isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Synthesis, antiviral, and anti-HIV-1 integrase activities of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines.

HIV-1 integrase (IN) is an essential enzyme for effective viral replication and is an attractive target for selective blockade of viral infection. Previously, we identified a series of sulfones, sulfonamides, and mercaptosalicylhydrazides (MBSAs) as IN inhibitors with antiviral activities in cell-based assays. In an effort to optimize a series of our active site directed lead compounds, we designed and synthesized novel benzodithiazines starting from MBSAs.

2-Amino-6-(1-imidazolylmethyl)-4-(3,5,5-trimethyl-2-pyrazolin-1-yl)-1,3,5-triazine and 2-amino-6-(1-benzimidazolylmethyl)-4-(3,5,5-trimethyl-2-pyrazolin-1-yl)-1,3,5-triazine hemihydrate.

The two title compounds, C(13)H(18)N(8) and C(17)H(20)N(8).0.5H(2)O, possess similar molecular shapes, with the pyrazoline moiety and s-triazine ring located approximately in one plane, and the imidazole or benzimidazole ring nearly perpendicular to the s-triazine nucleus.

Synthesis, structural characterization and in vitro antitumor activity of 4-dimethylaminopyridinium (6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides.

Previously, we have described a novel series of low molecular weight cancer-specific antitumor agents with aminium N-(1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidate structure. In an attempt to determine some of the structural features that account for the cytotoxic activity of such aminium salts, a novel series of 4-dimethylaminopyridinium (1,1-dioxo-1,4,2-benzodithiazin-3-yl)methanides (6-19) has been synthesized by the reactions of 3-methylthio-1,4,2-benzodithiazine1,1-dioxides with 4-DMAP and some active methylene compounds. The in vitro antitumor activity of these compounds has been tested in the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed.

Synthesis, structural characterization and in vitro antitumor activity of novel 6-chloro-1,1-dioxo-1,4,2-benzodithiazie derivatives.

A series of nonconventional aminium N-(6-chloro-7-R-1,1-dioxo-1,4,2-benzodithiazin-3-yl)arylsulfonamidates 7-15 have been synthesized by the reactions of 6-chloro-7-R-3-methylthio-1,4,2-benzodithiazine 1,1-dioxides with 4-dimethylaminopyridine or Et(3)N and some arylsulfonamides. The free N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)benzenesulfonamides 16-18 were obtained by treatment of their aminium salts with H(2)SO(4) in boiling acetic acid. The in vitro antitumor activity of the compounds 9, 11-14 and 16-18 has been tested in the antitumor screening of the National Cancer Institute (NCI), and relationships between structure and antitumor activity are discussed.

A new type of mixed anhydride and its applications to the synthesis of 7-substituted 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazines with in vitro antitumor activity.

A new series of 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine derivatives 8-25 with heteroaryloxycarbonyl or heteroarylcarbamoyl substituents at position 7 have been synthesized as potential antitumor agents. In this procedure a novel type of mixed anhydride 7 was prepared from 8-chloro-5,5-dioxoimidazo[1,2-b][1,4,2]benzodithiazine-7-carboxylic acid 6 and methanesulfonyl chloride, which in turn was condensed either with heteroarylamines or heteroarylhydroxy compounds. All the compounds prepared were screened at the National Cancer Institute (NCI) for their activities against a panel of 60 tumor cell lines, and relationships between structure and antitumor activity in vitro are discussed.