title: New bis-N9-(methylphenylmethyl)purine derivatives: synthesis and antitumor activity.
abstract: A series of ortho-, meta- and para-bis-N9-(methylphenylmethyl)purine derivatives 4-15 were obtained by two-step synthesis from various substituted chloropurines with alpha,alpha'-dichloroxylenes. These bis-N9-(methylphenylmethyl)purines 4-15 were evaluated for the primary cytotoxic activity against a panel of NCI-H460 (lung), MCF-7 (breast) and SF-268 (CNS) cancer cell lines. The 'active' compounds which reduced growth of cancer cells to ca. 32% or less, have been evaluated in a full panel of 60 human cancer cell lines over a 5-log dose range at the National Cancer Institute, Bethesda, MD. In this series, the most activity is correlated to the compounds derived from the 2,6-dichloropurines such as bis-9-[o-(methylphenylmethyl)]2,6-dichloropurine (5), bis-9-[m-(methylphenylmethyl)]2,6-dichloropurine (8), and bis-9-[p-(methylphenylmethyl)]2,6-dichloropurine (11). In particular compound 8 exhibited high sensitivity in leukemia cell lines and compounds 5, 8 and 11 exhibited consistent high sensitivity in many breast cancer cell lines. Compound 11 was the most potent in this series and exhibited GI(50)<0.01 microM sensitivity against non-small lung cancer EKVX, colon cancer HT-29, melanoma SK-MEL-28, renal cancer RXF 393, prostate cancer DU-145 and several breast cancer HS 578T and BT-549 cell lines.
authors.affiliation: Xavier University of Louisiana, College of Pharmacy, Division of Basic Pharmaceutical Sciences, 1 Drexel Drive, New Orleans, LA 70125, USA.
authors.forename: Nageswara
authors.initials: N
authors.lastname: Kode
authors.forename: Liying
authors.initials: L
authors.lastname: Chen
authors.forename: Devangachinta
authors.initials: D
authors.lastname: Murthy
authors.forename: Dare
authors.initials: D
authors.lastname: Adewumi
authors.forename: Shashikant
authors.initials: S
authors.lastname: Phadtare
mesh_terms: D000478:Alkylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011687:Purines