Τίτλος:
Discovery of steroidal lactam conjugates of POPAM-NH2 with potent anticancer activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2. © 2019 Newlands Press.
Συγγραφείς:
Trafalis, D.
Dalezis, P.
Geromichalou, E.
Sagredou, S.
Sflakidou, E.
Voura, M.
Grammatikopoulou, M.
Gabriel, C.
Sarli, V.
Περιοδικό:
Future Medicinal Chemistry
Εκδότης:
Future Medicine Ltd
Λέξεις-κλειδιά:
es 45; lactam derivative; melphalan; mg 144; steroid; unclassified drug; 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid; aniline mustard; antineoplastic agent; lactam; propionic acid derivative; steroid, animal cell; animal experiment; animal model; antineoplastic activity; apoptosis; Article; controlled study; drug potency; female; flow cytometry; human; human cell; IC50; in vitro study; in vivo study; LD50; leukemia; male; mouse; nonhuman; ovary adenocarcinoma; priority journal; animal; cell cycle; cell proliferation; chemistry; dose response; drug development; drug effect; drug screening; experimental neoplasm; HT-29 cell line; intraperitoneal drug administration; metabolism; pathology; SCID mouse; structure activity relation, Aniline Mustard; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Proliferation; Dose-Response Relationship, Drug; Drug Discovery; Drug Screening Assays, Antitumor; Female; HT29 Cells; Humans; Injections, Intraperitoneal; Lactams; Male; Mice; Mice, SCID; Neoplasms, Experimental; Propionates; Steroids; Structure-Activity Relationship
DOI:
10.4155/fmc-2019-0255
