Effect of 1-(phenyl)-N'-(4-methoxybenzylidene)-9H-pyrido[3,4-b] indole-3-carbohydrazide on in vitro poliovirus replication.

The effect of the alkaloid 1-(phenyl)-N'-(4-methoxybenzylidene)- 9H-pyrido[3,4-b]indole-3-carbohydrazide (PMC) on the poliovirus (PV) replication cycle in Vero cells was assayed by inhibition of the cytopathic effect (CPE) and inhibition of plaque forming units (PFU). Both methodologies suggested that the mode of action was avoidance of infection progression in the host cell. The compound was able to prevent CPE and PFU formation when the cells were pretreated with PMC for 24 h prior to PV infection. In addition, when the alkaloid was continuously maintained in the infected cultures, the spread of PV to adjacent cells was impaired. The pre-exposure and post-exposure prophylactic applications are possible situations in which an anti-PV drug might be used. Future studies are needed to elucidate the PMC mode of action and verify the feasibility of PMC use in vivo. No antipicornavirus agent is currently approved for clinical use.

Synthesis and antitumor activity of ß-carboline 3-(substituted-carbohydrazide) derivatives.

A series of ß-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The ß-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of ß-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 µM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 µM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) beta-carboline derivatives.

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.