title: CoMFA/CoMSIA 3D-QSAR of pyrimidine inhibitors of Pneumocystis carinii dihydrofolate reductase.
abstract: Pneumocystis carinii is typically a non-pathogenic fungus found in the respiratory tract of healthy humans. However, it may cause P. carinii pneumonia (PCP) in people with immune deficiency, affecting mainly premature babies, cancer patients and transplant recipients, and people with acquired immunodeficiency syndrome (AIDS). In the latter group, PCP occurs in approximately 80% of patients, a major cause of death. Currently, there are many available therapies to treat PCP patients, including P. carinii dihydrofolate reductase (PcDHFR) inhibitors, such as trimetrexate (TMX), piritrexim (PTX), trimethoprim (TMP), and pyrimethamine (PMT). Nevertheless, the high percentage of adverse side effects and the limited therapeutic success of the current drug therapy justify the search for new drugs rationally planned against PCP. This work focuses on the study of pyrimidine inhibitors of PcDHFR, using both CoMFA and CoMSIA 3D-QSAR methods.
authors.affiliation: Laboratório de Modelagem Molecular, Departamento de Síntese Orgânica, Instituto de Tecnologia em Fármacos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250, Rio de Janeiro, RJ, Brazil. osvaldofilho@far.fiocruz.br
authors.forename: Osvaldo A
authors.initials: OA
authors.lastname: Santos-Filho
authors.forename: Delphine
authors.initials: D
authors.lastname: Forge
authors.forename: Lucas V B
authors.initials: LV
authors.lastname: Hoelz
authors.forename: Guilherme B L
authors.initials: GB
authors.lastname: de Freitas
authors.forename: Thiago O
authors.initials: TO
authors.lastname: Marinho
authors.forename: Jocley Q
authors.initials: JQ
authors.lastname: Araújo
authors.forename: Magaly G
authors.initials: MG
authors.lastname: Albuquerque
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: de Alencastro
authors.forename: Nubia
authors.initials: N
authors.lastname: Boechat
mesh_terms: D020134:Catalytic Domain; D005493:Folic Acid Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D045363:Pneumocystis carinii / Q000201:enzymology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*
chemical_list: D005493:Folic Acid Antagonists; D011743:Pyrimidines; D013762:Tetrahydrofolate Dehydrogenase