Synthesis and cytotoxic evaluation of benzoxazole/benzothiazole-2-imino-coumarin hybrids and their coumarin analogues as potential anticancer agents.

Two series of 2-imino-coumarin based hybrids: 3-(benzoxazol-2-yl)-2H-chromen-2-imines 3-9 (series A-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 10-16 (series A-II), as well as their coumarin analogues: 3-(benzoxazol-2-yl)-2H-chromen-2-ones 17-21 (series B-I) and 3-(benzothiazol-2-yl)-2H-chromen-2-ones 22-28 (series B-II) were prepared as potential antitumor agents. The in vitro cytotoxic potency of the synthesized compounds was evaluated against five human cancer cell lines: DAN-G, A-427, LCLC-103H, RT-4 and SISO, and relationships between structure and anticancer activity are discussed. Among the compounds tested, 3-(benzo[d] oxazol-2-yl)-N,N-diethyl-2-imino-2H-chromen-7-amine (6, series A-I) and 3-(benzo[d]thiazol-2-yl)-6-fluoro-2H-chromen-2-one (26, series B-II) exhibited the most potent cytotoxic activity with IC50 values ranging from <0.01 µM to 1.1 µM. In particular, compound 6 demonstrated remarkable cytotoxicity against the A-427 ovarian cancer, the lung cancer LCLC-103H, urinary bladder cancer RT-4 and cervical cancer SISO cell lines with IC50 <0.01-0.30µM, inducing apoptosis in two representative cell lines.

Synthesis and in vitro anticancer and anti-HIV evaluation of new 2-mercaptobenzenesulfonamides.

The reactions of 6-chloro-3-methylthio-1,4,2-benzodithiazine 1,1-dioxide derivatives with appropriate diamines were investigated. Depending on the reaction conditions 2-mercaptobenzenesulfonamide derivatives or their oxidation product disulfides were obtained. All the compounds were tested at the US National Cancer Institute (Bethesda) for their in vitro anticancer and anti-HIV activities. The highest sensibility against leukemia cell lines was found for bis[2-(6-chloro-4-phenyl-3,4-dihydroquinazolin-2-yl)aminosulfonyl-5-chloro-4-(4-R2-phenylcarbamoyl)phenyl]disulfides (R2 = H or Cl). The results of anti-HIV tests displayed moderate activity of N-(pirydo[3,2-d]imidazol-2-yl)-2-mercaptobenzenesulfonamide.

Synthesis of some 2-hydroxy-1-[(4-chloro-2-mercaptophenyl)sulfonyl]imidazole derivatives with potential anticancer activity.

Several 2-(hydroxy or alkoxy)-1-[(4-chloro-5-R1-2-mercaptophenyl)sulfonyl]limidazoles [II-VI, IX-XI] and bis ¿5-chloro-4-methyl-2-[(2-aryloxyimidazol-1-yl)sulfonyl]phenyl disulfides [XII-XV] were obtained by either the selective hydrolysis or alcoholysis of the appropriate 7-R1-8-chloroimidazo[1,2-b] [1,4,2]benzodithiazine 5,5-dioxides [Ia-d]. The structures of the products and their S-substituted derivatives [VII, VIII] were established on the basis of elemental analysis and spectral data (IR, 1H and 13C NMR). Preliminary screening data indicated that the investigated compounds [III, X, XII and XIII] exhibited weak [III, X], moderate [XII] or fairly high [XIII] activity against some human tumor cell lines (Table 1).

Synthesis of 1-amino-2-(4-chloro-2-mercaptobenzenesulfonyl)guanidine derivatives with potential pharmacological activity.

Syntheses of 1-amino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [Va-o], 1-benzylidencimino-3-R2-2-(4-chloro-2- mercaptobenzenesulfonyl)guanidines [X, XII-XIX] and N-(4-chlorobenzylidene)-N'-(6-chloro-7-methyl-l, 1-dioxo- 1,4,2-benzodithiazin-3-yl)hydrazine [XX] have been described. The moderate anticancer and weak anti-HIV activities were observed in vitro for compounds [Va, e.g]. The obtained compounds were evaluated for their in vitro antimycobacterial activity towards a strain of Mycobacterium tuberculosis H 37 Rv.

Syntheses of S,N-substituted 2-mercaptobenzenesulfonamide derivatives with potential pharmacological activity.

A series of [5-chloro-4-methyl-2-sulfamoylphenyl(thio or sulfonyl)]alkanoic acids [I-VI], their methyl esters [VII-XII] and hydrazides [XIII-XXI] were prepared. The treatment of the selected esters [VII-VIII, XI-XII] with appropriate biguanide hydrochlorides gave 4-chloro-5-methyl-2-[2-amino-6-R3-triazin-4-ylalkyl(thio or sulfonyl)]benzenesulfonamides [XXII-XXVII]. The anticancer activity was observed in vitro for compound [XXII].