Synthesis and cytotoxic activity of lipophilic sulphonamide derivatives of the benzo[ b ]thiophene 1,1-dioxide

Benzo[b]thiophenesulphonamide 1,1-dioxide derivatives inhibit tNOX activity in a redox state-dependent manner

“…Since this compound and BTS-1 have identical molecular sizes and capacities to interact through polar groups, hydrogen bonds and/ or hydrophobic interactions with putative receptor sites, activity of BTS-1 can be attributed to the C2 -C3 double bond reactivity. In agreement with this, the C3-methyl derivative of BTS-1 shows no cytotoxic activity (Villar et al, 2004), a result that can be attributed to its impaired reactivity towards thiol groups. Thus, the possibility that BTS derivatives exert their inhibitory action on tNOX activity by interacting with cysteines of the active sites for protein disulphide-thiol interchange should also be considered.…”

“…The synthesis of BTS-2 was carried out by the usual methods described for the synthesis of sulphonamide derivatives (Villar et al, 2004), that is, through the treatment of the sulphonyl chloride derivative with ammonia or amines (Scheme 1). The chlorosulphonyl derivative was obtained from the 6-aminobenzo [b]thiophene 1,1-dioxide by the Meerwein's method (Meerwein et al, 1957) (treatment of diazonium salts with sulphonyl chloride in the presence of cuprous chloride), and then treated with phenetylamine to give the BTS-2 (28.1% yield).…”

“…The putative implication of tNOX in BTS-induced ROS generation and the fact that some enzymes related with ROS control such as the glutathione reductase and the glutathione S-transferase present a hydrophobic pocket near their active site (Karplus and Schulz, 1989;Chern et al, 2000) led us to synthesise and analyse new derivatives of the benzo[b]thiophene 1,1-dioxide carrying hydrophobic substituents of different length and grade of flexibility on the sulphonamide group and, in some cases, a clear correlation between the lipophilicity (log P) and the cytotoxic effect of these compounds was observed (Villar et al, 2004). Here we describe the synthesis and cytotoxic activity of 6-[N-(2-phenylethyl)]benzo[b]thiophenesulphonamide 1,1-dioxide (BTS-2), a new BTS derivative with increased flexibility, high lipophilicity (log P ¼ 2.82) and a predicted low toxicity for its putative metabolites, and we show its ability to specifically inhibit the tNOX activity and the absolute dependence of this inhibition on the redox state of the tNOX.…”

<strong><em>In vitro </em>Antimicrobial activity of Newly Synthesized Monoazaphenothiazine Derivatives.</strong>

“…These moieties have shown diverse biological activities including tranquilizers [3], antiinflammatory [4], antimalarial [5], antipsychotic [6], antimicrobial [7], antitubercular [8], antitumour [9] etc. It has been reported that some phenothiazine derivatives inhibit intracellular replication of viruses including human immunodeficiency viruses (HIV) [10][11].…”

Synthesis, Characterization and Antimicrobial Activity of Some Substituted 2-((1h-Indol-4-Yl)oxy)-N'- Benzylideneacetohydrazide

“…They have been found to posses the pharmacological activities such as antimalarial [1] , anticancer [2] , antibacterial [3] , antifungal [4] , antitubercular [5] , antiinflammatory, antimicrobial [6] , and antiviral [7] , etc. They also serve as a back bone for the synthesis of various heterocyclic compounds.…”