Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase

Introduction: Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rodríguez, Juan Bautista, Szajnman, Sergio Hernán
Publicado:	2016
Materias:	Bisphosphonates Bone disorders Farnesyl pyrophosphate synthase Malaria Parasitic diseases Toxoplasma gondii Trypanosoma cruzi antiparasitic agent benzoindole derivative bisphosphonic acid derivative enzyme enzyme inhibitor farnesyl pyrophosphate synthase farnesyl pyrophosphate synthase inhibitor hydroxyapatite quinoline derivative salicylic acid derivative unclassified drug farnesyl diphosphate geranyltransferase isoprenoid phosphate sesquiterpene binding affinity binding site bone disease bone mineral cell organelle drug activity drug design drug mechanism drug potency drug structure drug targeting enzyme activity enzyme inhibition human nonhuman priority journal protein structure Review X ray crystallography antagonists and inhibitors Bone Diseases metabolism molecularly targeted therapy Parasitic Diseases parasitology pathology Antiparasitic Agents Diphosphonates Drug Design Enzyme Inhibitors Geranyltranstransferase Humans Molecular Targeted Therapy Polyisoprenyl Phosphates Sesquiterpenes
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17460441_v11_n3_p307_Rodriguez http://hdl.handle.net/20.500.12110/paper_17460441_v11_n3_p307_Rodriguez
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_17460441_v11_n3_p307_Rodriguez
record_format	dspace
spelling	paper:paper_17460441_v11_n3_p307_Rodriguez2023-06-08T16:28:24Z Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase Rodríguez, Juan Bautista Szajnman, Sergio Hernán Bisphosphonates Bone disorders Farnesyl pyrophosphate synthase Malaria Parasitic diseases Toxoplasma gondii Trypanosoma cruzi antiparasitic agent benzoindole derivative bisphosphonic acid derivative enzyme enzyme inhibitor farnesyl pyrophosphate synthase farnesyl pyrophosphate synthase inhibitor hydroxyapatite quinoline derivative salicylic acid derivative unclassified drug antiparasitic agent bisphosphonic acid derivative enzyme inhibitor farnesyl diphosphate geranyltransferase isoprenoid phosphate sesquiterpene binding affinity binding site bone disease bone mineral cell organelle drug activity drug design drug mechanism drug potency drug structure drug targeting enzyme activity enzyme inhibition human nonhuman priority journal protein structure Review X ray crystallography antagonists and inhibitors Bone Diseases metabolism molecularly targeted therapy Parasitic Diseases parasitology pathology Antiparasitic Agents Bone Diseases Diphosphonates Drug Design Enzyme Inhibitors Geranyltranstransferase Humans Molecular Targeted Therapy Parasitic Diseases Polyisoprenyl Phosphates Sesquiterpenes Introduction: Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid farnesyl diphosphate. This molecule is the obliged precursor for the biosynthesis of sterols, ubiquinones, dolichols, heme A, and prenylated proteins. The blockade of FPPS prevents the synthesis of farnesyl diphosphate and the downstream essential products. Due to its crucial role in isoprenoid biosynthesis, this enzyme has been winnowed as a molecular target for the treatment of different bone disorders and to control parasitic diseases, particularly, those produced by trypanosomatids and Apicomplexan parasites.Areas covered: This article discusses some relevant structural features of farnesyl pyrophosphate synthase. It also discusses the precise mode of action of relevant modulators, including both bisphosphonate and non-bisphosphonate inhibitors and the recent advances made in the development of effective inhibitors of the enzymatic activity of this target enzyme.Expert opinion: Notwithstanding their lack of drug-like character, bisphosphonates are still the most advantageous class of inhibitors of the enzymatic activity of farnesyl pyrophosphate synthase. The poor drug-like character is largely compensated by the high affinity of the bisphosphonate moiety by bone mineral hydroxyapatite in humans. Several bisphosphonates are currently in use for the treatment of a variety of bone disorders. Currently, the great prospects that bisphosphonates behave as antiparasitic agents is due to their accumulation in acidocalcisomes, organelles with equivalent composition to bone mineral, hence facilitating their antiparasitic action. © 2016 Taylor & Francis. Fil:Rodriguez, J.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Szajnman, S.H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17460441_v11_n3_p307_Rodriguez http://hdl.handle.net/20.500.12110/paper_17460441_v11_n3_p307_Rodriguez
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Bisphosphonates Bone disorders Farnesyl pyrophosphate synthase Malaria Parasitic diseases Toxoplasma gondii Trypanosoma cruzi antiparasitic agent benzoindole derivative bisphosphonic acid derivative enzyme enzyme inhibitor farnesyl pyrophosphate synthase farnesyl pyrophosphate synthase inhibitor hydroxyapatite quinoline derivative salicylic acid derivative unclassified drug antiparasitic agent bisphosphonic acid derivative enzyme inhibitor farnesyl diphosphate geranyltransferase isoprenoid phosphate sesquiterpene binding affinity binding site bone disease bone mineral cell organelle drug activity drug design drug mechanism drug potency drug structure drug targeting enzyme activity enzyme inhibition human nonhuman priority journal protein structure Review X ray crystallography antagonists and inhibitors Bone Diseases metabolism molecularly targeted therapy Parasitic Diseases parasitology pathology Antiparasitic Agents Bone Diseases Diphosphonates Drug Design Enzyme Inhibitors Geranyltranstransferase Humans Molecular Targeted Therapy Parasitic Diseases Polyisoprenyl Phosphates Sesquiterpenes
spellingShingle	Bisphosphonates Bone disorders Farnesyl pyrophosphate synthase Malaria Parasitic diseases Toxoplasma gondii Trypanosoma cruzi antiparasitic agent benzoindole derivative bisphosphonic acid derivative enzyme enzyme inhibitor farnesyl pyrophosphate synthase farnesyl pyrophosphate synthase inhibitor hydroxyapatite quinoline derivative salicylic acid derivative unclassified drug antiparasitic agent bisphosphonic acid derivative enzyme inhibitor farnesyl diphosphate geranyltransferase isoprenoid phosphate sesquiterpene binding affinity binding site bone disease bone mineral cell organelle drug activity drug design drug mechanism drug potency drug structure drug targeting enzyme activity enzyme inhibition human nonhuman priority journal protein structure Review X ray crystallography antagonists and inhibitors Bone Diseases metabolism molecularly targeted therapy Parasitic Diseases parasitology pathology Antiparasitic Agents Bone Diseases Diphosphonates Drug Design Enzyme Inhibitors Geranyltranstransferase Humans Molecular Targeted Therapy Parasitic Diseases Polyisoprenyl Phosphates Sesquiterpenes Rodríguez, Juan Bautista Szajnman, Sergio Hernán Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
topic_facet	Bisphosphonates Bone disorders Farnesyl pyrophosphate synthase Malaria Parasitic diseases Toxoplasma gondii Trypanosoma cruzi antiparasitic agent benzoindole derivative bisphosphonic acid derivative enzyme enzyme inhibitor farnesyl pyrophosphate synthase farnesyl pyrophosphate synthase inhibitor hydroxyapatite quinoline derivative salicylic acid derivative unclassified drug antiparasitic agent bisphosphonic acid derivative enzyme inhibitor farnesyl diphosphate geranyltransferase isoprenoid phosphate sesquiterpene binding affinity binding site bone disease bone mineral cell organelle drug activity drug design drug mechanism drug potency drug structure drug targeting enzyme activity enzyme inhibition human nonhuman priority journal protein structure Review X ray crystallography antagonists and inhibitors Bone Diseases metabolism molecularly targeted therapy Parasitic Diseases parasitology pathology Antiparasitic Agents Bone Diseases Diphosphonates Drug Design Enzyme Inhibitors Geranyltranstransferase Humans Molecular Targeted Therapy Parasitic Diseases Polyisoprenyl Phosphates Sesquiterpenes
description	Introduction: Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid farnesyl diphosphate. This molecule is the obliged precursor for the biosynthesis of sterols, ubiquinones, dolichols, heme A, and prenylated proteins. The blockade of FPPS prevents the synthesis of farnesyl diphosphate and the downstream essential products. Due to its crucial role in isoprenoid biosynthesis, this enzyme has been winnowed as a molecular target for the treatment of different bone disorders and to control parasitic diseases, particularly, those produced by trypanosomatids and Apicomplexan parasites.Areas covered: This article discusses some relevant structural features of farnesyl pyrophosphate synthase. It also discusses the precise mode of action of relevant modulators, including both bisphosphonate and non-bisphosphonate inhibitors and the recent advances made in the development of effective inhibitors of the enzymatic activity of this target enzyme.Expert opinion: Notwithstanding their lack of drug-like character, bisphosphonates are still the most advantageous class of inhibitors of the enzymatic activity of farnesyl pyrophosphate synthase. The poor drug-like character is largely compensated by the high affinity of the bisphosphonate moiety by bone mineral hydroxyapatite in humans. Several bisphosphonates are currently in use for the treatment of a variety of bone disorders. Currently, the great prospects that bisphosphonates behave as antiparasitic agents is due to their accumulation in acidocalcisomes, organelles with equivalent composition to bone mineral, hence facilitating their antiparasitic action. © 2016 Taylor & Francis.
author	Rodríguez, Juan Bautista Szajnman, Sergio Hernán
author_facet	Rodríguez, Juan Bautista Szajnman, Sergio Hernán
author_sort	Rodríguez, Juan Bautista
title	Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
title_short	Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
title_full	Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
title_fullStr	Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
title_full_unstemmed	Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase
title_sort	approaches for designing new potent inhibitors of farnesyl pyrophosphate synthase
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17460441_v11_n3_p307_Rodriguez http://hdl.handle.net/20.500.12110/paper_17460441_v11_n3_p307_Rodriguez
work_keys_str_mv	AT rodriguezjuanbautista approachesfordesigningnewpotentinhibitorsoffarnesylpyrophosphatesynthase AT szajnmansergiohernan approachesfordesigningnewpotentinhibitorsoffarnesylpyrophosphatesynthase
_version_	1768544840580071424

Approaches for Designing new Potent Inhibitors of Farnesyl Pyrophosphate Synthase

Ejemplares similares