Twenty novel aminophosphonates derivatives (5a-5j and 6a-6j) conjugated irinotecan were synthesized through esterification reaction, and evaluated their anticancer activities using MTT assay. In vitro evaluation revealed that they displayed similar or superior cytotoxicity compared to the positive drug irinotecan against A549, MCF-7, SK-OV-3, MG-63, U2OS and multidrug-resistant (MDR) SK-OV-3/CDDP cancer cell lines. Among them, 9b displayed the most potent activity, with IC values of 0.92-3.23 μM against five human cancer cells, which exhibited a 5.4-19.1-fold increase in activity compared to the reference drug irinotecan, respectively. Moreover, cellular mechanism studies suggested that 9b arrested cell cycle at S stage and induced cell apoptosis along with the decrease of mitochondrial membrane potential (MMP). Interestingly, 9b significantly inhibited tumor growth in SK-OV-3 xenograft models in vivo without apparent toxicity, which was better than the positive drug irinotecan. Taken together, 9b possessed potent antitumor activity and may be a promising candidate for the potential treatment of human ovarian cancer cells.Copyright © 2020 Elsevier Masson SAS. All rights reserved.
High-protein diet more effectively reduces hepatic fat than low-protein diet despite lower autophagy and FGF21 levels.
July 13, 2020
IMPLEMENTATION OF A DEDICATED ENHANCED RECOVERY AFTER SURGERY (ERAS) PROGRAM FOR RADICAL CYSTECTOMY PATIENTS IS ASSOCIATED WITH DECREASED POSTOPERATIVE INPATIENT OPIOID USAGE AND PAIN SCORES.
June 1, 2020
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