Synthesis and antitumor activity of cis-dichloridoplatinum(II) complexes of 1,1′-biisoquinolines

• Published in: European journal of medicinal chemistry Vol. 45; no. 1; pp. 55 - 62
• Main Authors: Kuo, Chen-Yuan, Wu, Ming-Jung, Lin, Chu-Chieh
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 2010; Elsevier
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Biisoquinoline; Biological and medical sciences; Bischler – Napieralski; Cell Line, Tumor; Chemistry, Medicinal; General aspects; Humans; Imines - chemistry; Inhibitory Concentration 50; Isoquinolines - chemistry; Life Sciences & Biomedicine; Medical sciences; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Biisoquinoline; Antitumor activity; Bischler – Napieralski; Bischler - Napieralski; ISOQUINOLINE; Antineoplastic agent; Human; Divalent metal Complexes; Isoquinoline derivatives; Liver; Transition metal Complexes; Uterine cervix; In vitro; Hela cell line; Biological activity; Cell line; Chloro complex; Colon; Chemical synthesis; Tumor cell; Platinum II Complexes
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.09.023

A simple approach to 1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinolines is described. Reaction of phenethylamines with oxalyl chloride led to N,N′-bis(phenethyl) oxamides ( 1). Cyclization of oxamides by using Bischler – Napieralski conditions gave 3,3′,4,4′-tetrahydro-1,1′-biisoquinoline( 3) and unusual products 2, 4, 5. Reduction of 3,3′,4,4′-tetrahydro-1,1′-biisoquinolines with sodium boron hydride gave both rac-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinolines( 6) and meso-1,1′,2,2′,3,3′,4,4′ -octahydro-1,1′-biisoquinolines( 7). Compound 6 was resolved to (1S, 1S′) (8) and (1R, 1R′) (9) furtherly. By treating all the biisoquinolines with K 2PtCl 4 afforded their cis-dichloridoplatinum (II) complexes ( 12–18). The antitumor activity of these complexes was evaluated. [Display omitted] A simple approach to 1,1’,2,2’,3,3’,4,4’-octahydro-1,1’- biisoquinolines is described. Treatment all the biisoquinolines with K 2PtCl 4 afforded their cis-dichloridoplatinum (II) complexes . The antitumor activity of these complexes was evaluated.