Dataset Information

Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A.

ABSTRACT: We report here that des-methyl, des-amino pateamine A (DMDA-PatA), a structurally simplified analogue of the marine natural product pateamine A, has potent antiproliferative activity against a wide variety of human cancer cell lines while showing relatively low cytotoxicity against nonproliferating, quiescent human fibroblasts. DMDA-PatA retains almost full in vitro potency in P-glycoprotein-overexpressing MES-SA/Dx5-Rx1 human uterine sarcoma cells that are significantly resistant to paclitaxel, suggesting that DMDA-PatA is not a substrate for P-glycoprotein-mediated drug efflux. Treatment of proliferating cells with DMDA-PatA leads to rapid shutdown of DNA synthesis in the S phase of the cell cycle. Cell-free studies show that DMDA-PatA directly inhibits DNA polymerases ? and ? in vitro albeit at concentrations considerably higher than those that inhibit cell proliferation. DMDA-PatA shows potent anticancer activity in several human cancer xenograft models in nude mice, including significant regressions observed in the LOX and MDA-MB-435 melanoma models. DMDA-PatA thus represents a promising natural product-based anticancer agent that warrants further investigation.

SUBMITTER: Kuznetsov G

PROVIDER: S-EPMC3026899 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A.

Kuznetsov Galina G Xu Qunli Q Rudolph-Owen Lori L Tendyke Karen K Liu Junke J Towle Murray M Zhao Nanding N Marsh Joanne J Agoulnik Sergei S Twine Natalie N Parent Lana L Chen Zhihong Z Shie Jue-Lon JL Jiang Yimin Y Zhang Huiming H Du Hong H Boivin Roch R Wang Yuan Y Romo Daniel D Littlefield Bruce A BA

Molecular cancer therapeutics 20090505 5

We report here that des-methyl, des-amino pateamine A (DMDA-PatA), a structurally simplified analogue of the marine natural product pateamine A, has potent antiproliferative activity against a wide variety of human cancer cell lines while showing relatively low cytotoxicity against nonproliferating, quiescent human fibroblasts. DMDA-PatA retains almost full in vitro potency in P-glycoprotein-overexpressing MES-SA/Dx5-Rx1 human uterine sarcoma cells that are significantly resistant to paclitaxel, ...[more]

PMID: 19417157

Similar Datasets

Project description:Nucleoside analogues are among the most successful bioactive classes of druglike compounds in pharmaceutical chemistry as they are well-known for their numerous effective bioactivities in humans, especially as antiviral and anticancer agents. Coronavirus disease 2019 (COVID-19) is still untreatable, with its causing virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak havoc on the ground everywhere. This complicated international situation urged all concerned scientists, including medicinal chemists and drug discoverers, to search for a potent anti-COVID-19 drug. Cordycepin (3'-deoxyadenosine) is a known natural adenosine analogue of fungal origin, which could also be synthetically produced. This bioactive phytochemical compound is characterized by several proven strong pharmacological actions that may effectively contribute to the comprehensive treatment of COVID-19, with the antiviral activities being the leading ones. Some new studies predicted the possible inhibitory affinities of cordycepin against the principal SARS-CoV-2 protein targets (e.g., SARS-CoV-2 spike (S) protein, main protease (Mpro) enzyme, and RNA-dependent RNA polymerase (RdRp) enzyme) based on the computational approach. Interestingly, the current research showed, for the first time, that cordycepin is able to potently inhibit the multiplication of the new resistant strains of SARS-CoV-2 with a very minute in vitro anti-SARS-CoV-2 EC50 of about 2 μM, edging over both remdesivir and its active metabolite GS-441524. The ideal pharmacophoric features of the cordycepin molecule render it a typical inhibitor of SARS-CoV-2 replication, with its flexible structure open for most types of derivatization in the future. Briefly, the current findings further support and suggest the repurposing possibility of cordycepin against COVID-19 and greatly encourage us to confidently and rapidly begin its preclinical/clinical evaluations for the comprehensive treatment of COVID-19.

Dataset Information

Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A.

Publications

Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets