Thrombosis, which seriously endangers human health and life, is the leading cause of morbidity and mortality globally. Antithrombotic drugs can interfere with the occurrence and development of thrombotic diseases and play an important role in the treatment of thrombotic diseases. However, unsatisfactory efficacy and serious adverse effects of existing antithrombotic drugs increase the research for new, efficient and safer drugs. Natural and synthetic coumarins have been shown to possess antithrombotic activity, namely, anticoagulation and antiplatelet aggregation. Especially, coumarin-based warfarin, phenprocoumon and cloricromen have long been used in clinical treatment of thrombosis. Coumarin with low toxicity is the privileged structure for developing novel antithrombotic drugs with multiple mechanisms of action. The present review aims to compile current research on the development of coumarins against thrombosis, emphasizing the relationship between their chemical structures and therapeutic effectiveness. It is intended to provide promising ideas for the discovery of novel coumarin derivatives with high antithrombotic activity.

01 Nov 2019·Anticancer ResearchQ4 · MEDICINE

Oncolytic Effect of Adenoviruses Serotypes 5 and 6 Against U87 Glioblastoma Cancer Stem Cells

Q4 · MEDICINE

Article

Author: Potter, Ekaterina A ; Omigov, Vladimir V ; Taranov, Oleg S ; Efremov, Yaroslav R ; Grazhdantseva, Antonina A ; Razumov, Ivan A ; Bogachev, Sergey S ; Kochneva, Galina V ; Sizova, Mariya S ; Dolgova, Evgeniya V ; Ritter, Genrikh S ; Netesov, Sergey V ; Osipov, Ivan D ; Romanenko, Margarita V ; Bayborodin, Sergey I ; Proskurina, Anastasia S ; Zavyalov, Evgeniy L

BACKGROUND/AIMOncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells.MATERIALS AND METHODSOncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively.RESULTSAd6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group.CONCLUSIONAd6 was shown to be a promising agent for treating glioblastomas.

01 Jan 2016·Molecular Therapy - OncolyticsQ2 · MEDICINE

Evaluation of polymer shielding for adenovirus serotype 6 (Ad6) for systemic virotherapy against human prostate cancers

Q2 · MEDICINE

ArticleOA

Author: Catherine M Crosby ; Mary E Barry ; Tien V Nguyen ; Mallory A Turner ; Michael A Barry ; Greg J Heller

Oncolytic viruses hold promise as "self-amplifying" cancer therapies wherein a virally killed cell can produce thousands of new viral "drugs" that can kill more cancer cells. Adenoviruses (Ads) are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5). Unfortunately, most patients are already immune to Ad5 increasing the likelihood that the agent will be neutralized if used as a cancer therapy. In this work, lower seroprevalence Ad6 was tested as a systemic therapy for prostate cancer. Ad5 and Ad6 were injected intravenously a single time in nude mice bearing human prostate tumors, and toxicity and efficacy were assessed. Ad6 was chemically shielded with polyethylene glycol (PEG) to test if this would further improve its pharmacology. Ad6 produced 30-fold lower liver damage and less toxicity than Ad5. Ad6 significantly repressed the growth of androgen-resistant human DU145 prostate tumors and androgen-sensitive LNCaP tumors after single intravenous injection. PEGylation did not change virus distribution, but blunted liver damage and cytokine production by Ad6. PEGylated Ad6 eradicated LNCaP tumors and maintained body mass, but lost potency against the more challenging DU145 tumors. These and other data suggest that low seroprevalent Ad6 has better efficacy and safety than the benchmark oncolytic virus Ad5 for systemic therapy of prostate cancer. These data also indicate that PEGylation may improve Ad6 safety, but that this shielding may reduce oncolytic efficacy after intravenous treatment.

100 Deals associated with Cloricromen

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KEGG	Wiki	ATC	Drug Bank
D07139	Cloricromen	B01AC02	DB13367

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