Τίτλος:
Novel c(RGDyK)-based conjugates of POPAM and 5-fluorouracil for integrin-targeted cancer therapy
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Aim: Alkylating agents and antimetabolites are cytotoxic drugs commonly used in cancer treatment. These medications are often associated with serious side effects on normal tissues and organs. Methodology: To improve the pharmacological profile of the alkylating agent POPAM and the antimetabolite 5-fluorouracil, novel integrin-targeted delivery systems based on c(RGDyK) were successfully synthesized. The new conjugates were tested in vitro against different cancer cells such as PC3, SKOV3, A549, MCF7 and MBA-MB-321. Results & conclusion: The c(RGDyK) conjugates of POPAM demonstrated better inhibitory effects and selectivity compared with c(RGDyK) and POPAM. The c(RGDyK) conjugates of 5-FUA demonstrated diverse inhibitory effects compared with c(RGDyK) and 5-FUA related to the levels of integrin expression, the conjugate stability and sensitivity of cancer cells to 5-FUA. © 2017 2017 Future Science Ltd.
Συγγραφείς:
Thysiadis, S.
Katsamakas, S.
Dalezis, P.
Chatzisideri, T.
Trafalis, D.
Sarli, V.
Περιοδικό:
Future Medicinal Chemistry
Εκδότης:
Future Medicine Ltd
Λέξεις-κλειδιά:
3 (4 (bis (2 chloroethyl)amino)phenoxy)propanoic acid; alkylating agent; arginylglycylaspartic acid; c(RGDyK) conjugate; fluorouracil; integrin; unclassified drug; 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid; aniline mustard; antineoplastic agent; arginyl-glycyl-aspartic acid; cyclopeptide; fluorouracil; integrin; oligopeptide; propionic acid derivative, Article; carbon nuclear magnetic resonance; chemical procedures; chemical reaction; controlled study; cytotoxicity; drug transport; electrospray mass spectrometry; GI50; growth inhibition; human; human cell; IC50; liquid chromatography-mass spectrometry; molecular stability; molecularly targeted therapy; MTT assay; priority journal; protein binding; protein expression; proton nuclear magnetic resonance; reversed phase high performance liquid chromatography; thin layer chromatography; ultraviolet spectrophotometry; A-549 cell line; amino acid sequence; analogs and derivatives; antagonists and inhibitors; cell proliferation; chemistry; drug effects; high performance liquid chromatography; MCF-7 cell line; metabolism; neoplasm; nuclear magnetic resonance spectroscopy; pathology; tumor cell line, A549 Cells; Amino Acid Sequence; Aniline Mustard; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Chromatography, High Pressure Liquid; Fluorouracil; Humans; Integrins; Magnetic Resonance Spectroscopy; MCF-7 Cells; Neoplasms; Oligopeptides; Peptides, Cyclic; Propionates
DOI:
10.4155/fmc-2017-0139
