Synthesis and SAR of vinca alkaloid analogues
Matthew E. VossJeffery M. RalphDejian XieDavid D. ManningXinchao ChenAnthony J. FrankAndrew J. LeyhaneLei LiuJason M. StevensCheryl L. BuddeM. D. SurmanThomas FriedrichDenise PeaceIan L. ScottM. WolfRandall S. Johnson
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Vinca
HeLa
Vinca alkaloid
Cepharanthin (CE), a bisbenzylisoquinoline alkaloid drug, was tested in vitro and in vivo with chemotherapeutic agents, vincristine (VCR), vinblastine (VLB), and vindesine (VDS). The activity of these agents alone or in combination was tested against a human colon cancer cell line (RPMI 4788) or a human uterine cervical cancer cell line (HeLa), using a modified microcytotoxicity-viable cell staining assay. In the in vitro study, the antiproliferative activities of each vinca alkaloid were enhanced additively or synergistically by combination with CE in RPMI 4788 cells as well as HeLa cells. The sequential exposure of the RPMI 4788 cells or HeLa cells to both CE and each vinca alkaloid agent showed evidence of a more significant potentiation. The antiproliferative activity of the combination of each vinca alkaloid agent(VCR, VLB, or VDS) with CE was almost equivalent to the effect of each vinca alkaloid agent alone which was potentiated by CE tenfold through several hundredfold. In an experimental model of tumor growth and survival, in which RPMI 4788 cells were transplanted subcutaneously or intraperitoneally into BALB/c nu/nu mice respectively, CE (1 mg/kg) alone exerted not significant inhibitory activity against tumor growth or survival, and VCR (0.25 mg/kg) alone partially inhibited these antitumor activities. Furthermore, the antitumor effects of VCR were elevated synergistically by the simultaneous administration of CE. These studies indicate that due to their therapeutic potential, combinations of vinca alkaloid agent with CE might be a promising therapy for some human cancers.
Vinca
Vinca alkaloid
HeLa
Vindesine
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Vindoline
Vinca
Vinca alkaloid
Apocynaceae
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Vinca
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Vinca alkaloid
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Vinblastine an alkaloid of the periwinkleplant (Vinca), produced marked alterations in the motility of gastrointestinal tract in rats. The alkaloid reduced the rate of gastric emptying and slowed the transit of test substance through the small intestine. The effect of the drug on gastric emptying appeared to be dose-dependent. The latency of drug action on gut motility was found to be 5--10 min, when injected through the jugular vein.
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Vinca alkaloid
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Vinca
Apocynaceae
Vinca alkaloid
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The labeling for vinca alkaloid chemotherapy drugs is being revised to remove instructions for their administration with use of a syringe. This revision is in response to inadvertent intrathecal administration of vinca alkaloids, which is normally fatal.
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Vinca alkaloid
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Vinca Alkaloids XXXII. Microbiological conversions of vindoline, a major alkaloid from vinca rosea L
Abstract Vindoline, a major alkaloid from Vinca rosea L was subjected to microbiological conversion using Streptomyces cultures. Several new metabolites were isolated and their structures elucidated.
Vinca
Vindoline
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Vinca alkaloid
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Conophylline, a new vinca alkaloid isolated from the plant Ervatamia microphylla induced normal flat morphology in K-ras-NRK and K-ras-NIH cell lines, and lowered the increased uptake of 2-deoxyglucose in K-ras-NRK cells. Conophylline inhibited the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into nude mice. On the other hand, it showed no effect on survival of the mice loaded with L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkaloid that induced normal phenotypes in ras-expressing cells.
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Vinca alkaloid
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From the leaves of Vinca difformis, a new alkaloid, difforine, was isolated which was assignated structure 1 on the basis of spectroscopic evidence. Another alkaloid was identified as normacusine B 2.
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A new vinca alkaloid was isolated from a chroloform extract of Ervatamia microphylla leaves as a potent inhibitor of ras functions. The structure of the new alkaloid was elucidated by spectroscopic analysis to be a dimer of aspidosperma-class indoles. The new inhibitor, named III-121C, induced normal morphology in K-ras(ts)-NRK cells at around 0.3 microgram/ml. It also inhibited DNA, RNA, and protein synthesis weakly at 0.3 microgram/ml. It inhibited the growth of K-ras(ts)-NRK cells with IC50s of 0.29, and 0.20 microgram/ml at 33 degrees C and 39 degrees C, respectively. III-121C is the first vinca alkaloid that inhibits ras functions.
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