Disease relevance of Pmedap

• Also, (RS)-FPMPA and (RS)-FPMPDAP have a substantially higher therapeutic index in mice in inhibiting Moloney murine sarcoma virus-induced tumor formation and associated death and are markedly less inhibitory to human bone marrow cells than PMEA and PMEDAP [1].
• PMEDAP was highly active against HSV-1, HSV-2, and VZV in the concentration range (EC50) of 0.07-2 microg/mL [2].
• (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3'-dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes [3].
• Efficacy of oral 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) in the treatment of retrovirus and cytomegalovirus infections in mice [4].
• In particular, (R,S)-FPMPA and (R,S)-FPMPDAP showed a greater antiviral selectivity than PMEA and PMEDAP due to the virtual lack of toxicity of the former compounds in these cell systems [5].

High impact information on Pmedap

• Capillary electrophoresis separation of the new anti-AIDS agents 9-(2-phosphonylmethoxyethyl)adenine and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine in mixtures with some monoribonucleotides or the most common deoxynucleotides [6].
• These results are consistent with the observed antineoplastic activities of the parental guanine (PMEG) and 2,6-diaminopurine (PMEDAP) PME-derivatives [7].
• The medial inhibitory concentrations (IC50) of N(6)-nonsubstituted compounds range from 0.13 (PMEDAP) to 354 microM ((R)-PMPA) [8].
• The analogues selected for testing on human leukemia cell lines, namely 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine (PMEDAP), and 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) exhibited growth-inhibiting activity at low concentrations, and apoptosis-inducing activity at high concentrations [9].
• Genotoxic properties expressed as acquired chromosomal aberrations and induction of apoptosis after treatment with acyclic nucleoside phosphonates PMEG, PMEDAP and its N6-substituted derivatives Me2NEt-PMEDAP, allyl-PMEDAP, Me2-PMEDAP and cypr-PMEDAP, were studied in in vitro conditions [10].

Chemical compound and disease context of Pmedap

• 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) are selectively inhibitory to human immunodeficiency virus and other retroviruses [11].
• Also, PMEA and PMEDAP proved highly active against HHV-6 infection, whereas (S)-FPMPA and (R)-PMPDAP were inactive [12].
• However, PMEA, PMEDAP and PMEMAP showed marked and selective activity against the human immunodeficiency virus (HIV) [13].

Biological context of Pmedap

• These results indicate that PMEDAP application induces apoptosis in in vivo growing lymphomas [14].
• Thus, the diverse anticancer efficacy of PMEDAP treatment among SD/cub lymphomas could be associated with the different phenotypes of individual neoplasias [15].
• An increase of nuclear DNA fragmentation was found during PMEDAP administration compared with spontaneous DNA fragmentation of untreated control lymphomas [14].
• Significant concentration dependent inhibition of cell proliferation caused by PMEDAP and/or PMEA was also observed in murine splenocytes [16].
• Dose-dependent genotoxicity of both PMEDAP and PMEA was not observed in in vitro tests on stabilized diploid MRC-5 cell line [16].

Anatomical context of Pmedap

• Antitumour activity of N6-substituted PMEDAP derivatives against T-cell lymphoma [17].

Associations of Pmedap with other chemical compounds

• The mutant L1210/PMEA-1 cell line was characterized by an unusual specificity in that the cytostatic activity was severely impaired only for PMEA and the closely related 2,6-diaminopurine derivative PMEDAP, but not for its guanine counterpart PMEG or for 9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) [18].

Analytical, diagnostic and therapeutic context of Pmedap

• The efficacy of HPMPA, HPMPC, PMEA and PMEDAP has been demonstrated in various animal model infections, and the further pursuit of their clinical potential seems fully justified [19].
• Using the colorimetric method, we found that 50% effective concentration levels of several known anti-HBV agents (HPMPA, PMEDAP, PMEA and others) were similar to those reported in studies using Southern blot analysis [20].
• However, an increased proliferation was observed after treatment of the cell culture with very low dose of PMEDAP [10].

References