Synthesis and antimicrobial activity of some new substituted 9-[1H-pyrazolo[3,4-b] quinolin-1-YL] acridines

2-Chloro-6-methyl/methoxy-3-formylquinoline upon condensation with substituted 9- hydrazino-acridine afforded corresponding hydrazones which were cyclized under alkaline condition to give 9-[6-substituted-1H-pyrazolo[3,4-b]quinolin-1-yl] acridine analoges. All of the synthesized compounds were characterized by their elemental analysis, IR and NMR spectral studies. Biological screening of the prepared compounds have been screened on some strain of bacteria and fungus

Synthesis and antineoplastic activity of certain triazene and triazeno-acridine combilexin derivatives

Four series of bifunctional ligands have been synthesized as DNA-binding combilexins. These novel agents contain a triazeno-benzene sulfonamide linker moiety that is attached to an intercalating acridine or acridone chromophore by a functionalized amide or ester residue. In order to obtain these combilexins three series of the anticipated antitumor triazeno-benzene sulfonamide were synthesized. The synthesis and bioscreening of the new antineoplastic compounds are depending on the structural correlation with several reported antineoplastic acridines. 2-Chlorobenzoic acid was reacted with anthranilic acid to give N-[2-carboxyphenyl] anthranilic acid which upon cyclodehydration with sulfuric acid afforded 9-oxo-9, 10-dihydroacridine-4-carboxylic acid, [acridone-4-carboxylic acid] 8. This latter intermediate has been converted to 9-chloroacridine carbonyl chloride 9 using thionyl chloride. Selective substitution of 9 with derivatives of 4-[piperazine-l-yldiazenyl] benzenesulfonamides 4a-e or derivatives of 4-[2-hydroxyethyl] piperazine-l-yl]diazenyi] benzenesulfonamides 5a-e to yield their 9-chloroacridine-4-carboxamides 10a-e and 9-chloroacridine-4-carboxylic acid esters 13a-e respectively. Those intermediates have been reacted either with different sulfonamides to give derivatives of 4-[4-[4-[4 sulfamoylphenyldiazenyl] piperazine-l-carbonyl]-9-ylamino] benz-enesulfonamides 11a-h and derivatives of 2-[[4-[4-sulfamoyl-phenyl]diazenyl]piperazine-l-yl]ethyl 9-[4-sulfamoylphenyl-amino]-9,10-dihydroacridine-4-carboxylates 14a-i respectively or subjected to mild acid hydrolysis to yield derivatives of 4-[4-[[9-oxo-9,1 Q-dihydroacridine-4-carbonyl]piperazine-l-yl]diazenyl]-benzenesulfonamide 12a-e and derivatives of 2-[4-[[4-sulfamoyl-phenyl]diazenyl]piperazine-l-yl]ethyl-9-oxo-9,10-dihydroacridine-4-carboxylate 15a-e respectively. Besides, the synthesis of derivatives of 4-[piperazine-l-yldiazenyl] benzenesulfonamides 4a-e and derivatives of 4-[2-hydroxyethyl]piperazine-1-yl] diazenyl] benzenesulfonamides 5a-e has been achieved via diazotization of various substituted benzene sulfonamides with sodium nitrite and hydrochloric acid followed by various amines coupling to yield the target triazeno-benzene sulfonamides. Fourteen new compounds were selected for screening their antitumor activity against breast cell line in National Cancer Institute. Six of them were found to be active as antitumor agents, while two were found to be mild active

New antimicrobial 9-[p-heterocyclo-substituted anilino]-tetrahydroacridines

The chemistry of tetrahydroacridines is of continuous interest, as they are associated with pharmacological activities[1-9]. Some members of this class of compounds are used as memory-enhancing agents for treating Alzheimer disease [1, 2] acetylcholine esterase inhibitors[3-5], DNA-binding agents[6], antimicrobial agents[7] and as amoebicides[7-9]. The present work deals with the synthesis of a new series of 9-[p-[4-aryl- 3-cyano-2-iminopyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [3] and their 2-oxo-[or thioxo]-pyridinylanilino derivatives 4 and 5, besides other related products 7-12 to be evaluated against bacteria and fungi. Synthesis was achieved by allowing 9-chloro-1, 2, 3, 4-tetrahydroacridine [1][10] to react with p-aminoacetophenone to give the 9-[p-acetylanilino] derivative 2. The one pot reaction of 2 with malononitrile, ammonium acetate and the appropriate aromatic aldehyde afforded the corresponding 9-[p-[4-aryl-3-cyano-2-iminopyridin-6-yl]-anilino]-1, 2, 3, 4-tetrahydroacridines [3a-e], respectively [Route a]. Similarly, reaction of 2 with ethyl cyanoacetate, ammonium acetate and the appropriate aromatic aldehyde in n-butanol afforded the corresponding 9-[p-[4-aryl-3-cyano-2[1H]-oxo-pyridin-6-yl] anilino]-1, 2, 3, 4-tetrahydroacridines [4a-d], respectively. On the other hand, the reaction of an ethanolic mixture of 2 with substituted arylmethylene cyanothioacetanilides [5][11, 12] in the presence of ammonium acetate gave the corresponding 3-cyano-4-arylpyridin-2[1H]-thiones [6a-d], respectively [Route a]. Also reaction of 1 with ethyl-p-aminobenzoate gave the corresponding ethyl-p-[1, 2, 3, 4-tetra-hydroacridin-9-yl] aminobenzoate [7] which upon reaction with hydrazine hydrate afforded the corresponding acid hydrazide 8. [Route b]. In addition, acetylation of 2 was accomplished by heating it with ethyl acetate in the presence of sodium metal to give p-[[1, 2, 3, 4-tetrahydroacridin-9-yl]amino]acetylacetophenone [9]. Bromination of 2 afforded 9-[p-bromo-acetyl anilino]-1, 2, 3, 4-tetrahydroacridine [10] which upon reaction with thiourea gave the corresponding 9-[p-[2-aminothiazol-4-yl]aniline-1, 2, 3, 4-tetrahydroacridine [11] was hydrobromide salt, while reaction of 10 with malononitrile afforded p-[1, 2, 3, 4-tetrahydroacridin-9-yl]amino-benzoylmethyl malononitrile [12] [Route c]