title: Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents.
abstract: We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties.
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Brogi
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Joshi
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sanna Coccone
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Parapini
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy; Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università di Milano, Via Pascal, 36, 20133 Milan, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Basilico
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Farmacia, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy. Electronic address: campiani@unisi.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy. Electronic address: gemma@unisi.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.affiliation: European Research Centre for Drug Discovery and Development (NatSynDrugs), Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via Aldo Moro 2, 53100 Siena, Italy; Centro Interuniversitario di Ricerche sulla Malaria (CIRM), University of Perugia, Perugia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D003022:Clotrimazole / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D010963:Plasmodium falciparum / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D008024:Ligands; D003022:Clotrimazole
keywords: 3D-QSAR; Clotrimazole; Ligand-based; Malaria; Plasmodium falciparum