A new series of 2,3-diaryl-4/5-hydroxy-cyclopent-2-en-1-one analogues replacing the cis double bond of combretastatin A-4 (CA-4) by 4/5-hydroxy cyclopentenone moieties was designed and synthesized. The analogues displayed potent cytotoxic activity (IC50<1 microg/mL) against a panel of human cancer cell lines and endothelial cells. The most potent analogues 11 and 42 belonging to the 5-hydroxy cyclopentenone class were further evaluated for their mechanism of action. Both of the analogues led to cell cycle arrest at G2/M phase and induced apoptosis in endothelial cells. Antitubulin property of 42 was superior to 11 and comparable to CA-4. The compound 42 had better aqueous solubility, metabolic stability, and pharmacokinetic profile than CA-4 and also demonstrated significant tumor regression in the human colon xenograft model. Our data suggests that cis-restricted analogues of CA-4 are a new class of molecules that have the potential to be developed as novel agents for the treatment of cancer.
Abstract:The surgical and other biological instruments are made of Stainless Steel AISI 316L which lacks antimicrobial properties. Copper is coated on Stainless Steel substrate using DC Magnetron sputtering which is used to achieve required film of thickness (0.5-8µm). The deposition pressure, substrate temperature, power supply, distance between the specimen and target are optimized and maintained constant, while the sputtering time (30-110 minutes) is varied. The sputtered copper thin film's morphology, compositional is characterized by SEM and EDAX. X-ray diffraction analysis shows copper oriented on (111) and (002) and copper oxide on (111) planes. The contact angle of copper thin film is 92° while AISI316L shows 73°. The antimicrobial studies carried in Staphylococcus aureus, Escherichia Coli, Klebsiella pneumonia and Candida albicans shows that CFU/mL was reduced to 30 after 24 hours. The cell viability is studied by MTT assay test on Vero cell line for 24 hours, 48 hours and 72 hours and average cell viability is 43.85%. The copper release from the thin film to the culture medium is 4826µg/L (maximum) is estimated from AAS studies. The bacteria and fungi are found to be destroyed by the copper thin film but do not show much reaction with living Vero cells.
Surgical instruments and other bioimplant devices, owing to their importance in the biomedical industry require high biocompatibility to be used in the human body. Nevertheless, issues of compatibility, bacterial infections are quite common in such devices. Hence development of surface coatings on various substrates for implant applications is a promising technique to combat the issues arising in these implant materials. The present investigation aims at coating copper on stainless steel substrate using DC Magnetron sputtering which is used to achieve film of required thickness (0.5–8[Formula: see text][Formula: see text]m). The deposition pressure, substrate temperature, power supply, distance between the specimen and target are optimized and maintained constant, while the sputtering time (30–110[Formula: see text]min) is varied. The sputtered copper thin film’s morphology, composition are characterized by SEM and EDAX. X-ray diffraction analysis shows copper oriented on (111) and (002) and copper oxide on (111) planes. The contact angle of copper thin film is 92[Formula: see text] while AISI 316L shows 73[Formula: see text]. The antimicrobial studies carried in Staphylococcus aureus, Escherichia Coli, Klebsiella pneumonia and Candida albicans show that the maximum reduction was seen upto 35, 26, 54, 39[Formula: see text]CFU/mL, respectively after 24[Formula: see text]h. The cell viability is studied by MTT assay test on Vero cell line for 24[Formula: see text]h, 48[Formula: see text]h and 72[Formula: see text]h and average cell viability is 43.85%. The copper release from the thin film to the culture medium is 6691[Formula: see text][Formula: see text]g/L (maximum) is estimated from AAS studies. The copper coated substrate does not show much reaction with living Vero cells whereas the bacteria and fungi are found to be destroyed.
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