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Silica Nanoparticles for Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Bhat et al. functionalized the surface of anticoagulant-loaded MSN with a peptide containing a thrombin-specific cleavage sequence to delay the blood clotting process. Acenocoumarol was loaded into the MSN pores and then a LVPRGS containing peptide was attached to the surface through “click” chemistry, effectively preventing anticoagulant leakage prior to thrombin exposure. The enzymatic concentration needed to be at least 100 nM to trigger drug release (for reference, thrombin concentrations in human blood are ~1 nM under normal conditions and >500 nM during clot formation); hence, this system could remain dormant in the blood and become active only during coagulation. In rabbit blood plasma, the peptide functionalized MSN induced no coagulation, while in the presence of human thrombin, clotting was slowed from 2.6±0.3 min with just calcined MSN to 5.0±0.3 min with the thrombin triggered nanocomposite [75].
Fibrinolytic Enzymes for Thrombolytic Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Swaroop S. Kumar, Sabu Abdulhameed
Anticoagulants like coumarin derivatives were discovered in 1939 by the identification of dicumarol from spoiled sweet clover hay which is a vitamin K antagonist by Link and Campbell (Stahmann et al., 1941). Further studies on coumarin derivatives led to the discovery of warfarin which was initially used as rodenticide and later approved for clinical use as anticoagulant. It was the first oral thrombin inhibitor and found useful in preventing embolic strokes (Aguilar and Hart, 2005). Limitations of these vitamin K antagonists were bleeding complications, interaction with food, necrosis, and hair loss (Dantas et al., 2004; Ansell et al., 2008; Pirmohamed, 2006). Even though other coumarin derivatives such as phenprocoumon and acenocoumarol also were used as anticoagulants, warfarine is the most common vitamin K antagonist in practice and remains as affordable in cardiovascular disease management.
Direct Oral Anticoagulants: New Options
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
VKAs are synthetic derivatives of the natural compound dicoumarol. The latter is generated from melilotic acid in Melilotus officinalis by mildew and was responsible for the ‘sweet clover disease’ and the bleeding to death of cattle in Wisconsin in 1926. Clinically used VKAs are warfarin, phenprocoumon and less common acenocoumarol.
Synthesis and cytotoxic activity of some novel benzocoumarin derivatives under solvent free conditions
Published in Green Chemistry Letters and Reviews, 2019
Anhar Abdel-Aziem, Huda Refaat Mahmoud Rashdan, Entesar Mohamed Ahmed, Sara N. Shabaan
The organic solvents are volatile and harmful, causing risks to peoples who inhale them as well as the environment. Thus, development of less hazardous synthetic methods for organic reactions is one of our objectives in current research. The grinding method is one of green chemistry techniques as it is carried out in the absence of solvent (1–4). Moreover, the solvent-free reactions have numerous advantages: reduced pollution, low costs, high yields and purities of products (5, 6). Otherwise, many compounds which contain coumarin nucleus exhibit antimicrobial (7), analgesic (8), ulcerogenic (9), anticoagulant (10), antiviral (11) and anti-malarial (12), anti-inflammatory (13, 14) anti-leishmanial (15) as well as antioxidant (16, 17) activities. The anti-tumor activity of coumarins received a considerable interest owing to their cytotoxic activity against various types of cancer cells, including gastric cancer, liver cancer, colon cancer, breast cancer, prostate cancer, Periodontal Ligament, fibroblast, nasopharyngeal carcinoma, and normal fibroblast cell lines (18–22). In addition, coumarin derivatives can inhibit growth in human cancer cell lines (23) such as renal (ACHN), lung (A549, H727), leukemia (HL-60), breast (MCF7) and renal cell carcinoma (24). Coumarin and its derivatives are important components among the molecules in the drug industry. Warfarin, acenocoumarol and phenprocoumon are a derivatives of coumarin used as anticoagulant drugs. These are vitamin K antagonist which inhibits the coagulation via blocking of the coagulation factors [I, VII, IX and X] (25–27). Moreover, warfarin reduced metastases from intestinal cancer to a wide extent (28) and is also used beside the surgical treatment of cancer masses (29) (Figure 1).