ABSTRACT
A series of novel 11H-benzo[a]carbazole-5-carboxamide derivatives were designed, synthesized and evaluated for their antitumor activity against human cancer A549 and HCT-116 cell lines. Most of the compounds showed potent antitumor activities, and compound 8 displayed remarkable in vitro and in vivo anticancer activity comparable to that of amonafide.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Carbazoles/chemistry , Carbazoles/therapeutic use , Amides/chemical synthesis , Amides/chemistry , Amides/pharmacology , Amides/therapeutic use , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Carbazoles/chemical synthesis , Carbazoles/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Mice , Mice, Nude , Neoplasms/drug therapy , Structure-Activity RelationshipABSTRACT
PTD4-apoptin protein enters cells and harbors tumor-selective cell death activity. Dacarbazine is the mainstay of treatment for malignant melanoma. In this study, we investigated the cytotoxic effect of PTD4-apoptin protein and/or dacarbazine in mouse B16-F1 and human A875 and SK-MEL-5 melanoma cells in vitro and by means of a mouse B16-F1 melanoma model in vivo. PTD4-apoptin protein inhibits the growth of B16-F1, A875 and SK-MEL-5 melanoma cells in a dose-dependent manner, but not in normal human cell lines WI-38 and L-02. PTD4-apoptin combined with dacarbazine revealed a synergistic cytotoxic effect (coefficient of drug interaction<1) in all three different tumor cell lines. In vivo, PTD4-apoptin protein and dacarbazine alone effectively inhibited the growth of B16-F1 melanoma in C57BL/6 mice. Strikingly, combined PTD4-apoptin/dacarbazine treatment significantly increased the antitumor effect in comparison to the single treatments. As important, a combined PTD4-apoptin/dacarbazine treatment with a 50% reduction of dacarbazine revealed similar antitumor activities, without detectable hematologic side effects. A combined PTD4-apoptin/dacarbazine treatment represents a promising novel efficient and safe anticancer strategy.
Subject(s)
Capsid Proteins/pharmacology , Dacarbazine/pharmacology , Melanoma/drug therapy , Recombinant Fusion Proteins/chemistry , Animals , Antineoplastic Agents, Alkylating/pharmacology , Capsid Proteins/administration & dosage , Capsid Proteins/chemistry , Cell Line , Cell Line, Tumor , Drug Synergism , Female , Humans , Melanoma/pathology , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BLABSTRACT
A series of R and S enantiomers of 7-(3-methylpiperazin-1-yl) quinolone derivatives were synthesized from (R)- and (S)-tert-butyl 2-methylpiperazine-1-carboxylate and tested for their antibacterial activities on 14 kinds of bacteria. Although no distinct difference in in vitro antibacterial activities was observed, 2-64-fold difference between R and S enantiomers was observed in approximately 52% of cases.
Subject(s)
Piperazines/chemistry , Quinolones/chemical synthesis , Molecular Structure , Piperazines/chemical synthesis , StereoisomerismABSTRACT
Two new 18(13-->12)-abeo-lanostane triterpenoid acids, ananosic acids B (1) and C (2), were isolated from the stems of Kadsura anaosma. Their structures were elucidated by spectral studies and chemical transformation. Compounds 1 and 2 were evaluated for cytotoxicity using CCRF-CEM leukemia cells and HeLa cells.
