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Start Over Author "Cervi G" Journal bioorganic medicinal chemistry
3 results on '"Cervi G"'

1. Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases.

Author

Casuscelli F, Ardini E, Avanzi N, Casale E, Cervi G, D'Anello M, Donati D, Faiardi D, Ferguson RD, Fogliatto G, Galvani A, Marsiglio A, Mirizzi DG, Montemartini M, Orrenius C, Papeo G, Piutti C, Salom B, and Felder ER

Subjects
Drug Discovery, Humans, Molecular Docking Simulation, Protein Kinase Inhibitors chemical synthesis, Protein Structure, Tertiary, Proto-Oncogene Proteins c-pim-1 chemistry, Proto-Oncogene Proteins c-pim-1 metabolism, Pyrazines chemical synthesis, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins c-pim-1 antagonists & inhibitors, Pyrazines chemistry, Pyrazines pharmacology
Abstract

A novel series of PIM inhibitors was derived from a combined effort in natural product-inspired library generation and screening. The novel pyrrolo[1,2-a]pyrazinones initial hits are inhibitors of PIM isoforms with IC50 values in the low micromolar range. The application of a rational optimization strategy, guided by the determination of the crystal structure of the complex in the kinase domain of PIM1 with compound 1, led to the discovery of compound 15a, which is a potent PIM kinases inhibitor exhibiting excellent selectivity against a large panel of kinases, representative of each family. The synthesis, structure-activity relationship studies, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Furthermore, the cellular activities including inhibition of cell growth and modulation of downstream targets are also described., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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2. Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity.

Author

Bindi S, Fancelli D, Alli C, Berta D, Bertrand JA, Cameron AD, Cappella P, Carpinelli P, Cervi G, Croci V, D'Anello M, Forte B, Giorgini ML, Marsiglio A, Moll J, Pesenti E, Pittalà V, Pulici M, Riccardi-Sirtori F, Roletto F, Soncini C, Storici P, Varasi M, Volpi D, Zugnoni P, and Vianello P

Subjects
Animals, Antineoplastic Agents chemistry, Aurora Kinases, Cell Cycle drug effects, Cell Proliferation drug effects, Computational Biology, Crystallography, X-Ray, Drug Screening Assays, Antitumor, Enzyme Inhibitors chemistry, HL-60 Cells, Humans, Male, Mice, Mice, SCID, Models, Molecular, Molecular Dynamics Simulation, Molecular Structure, Neoplasms, Experimental drug therapy, Pyrazoles chemical synthesis, Pyrazoles chemistry, Stereoisomerism, Structure-Activity Relationship, Thiophenes chemical synthesis, Thiophenes chemistry, Transplantation, Heterologous, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors pharmacology, Protein Serine-Threonine Kinases antagonists & inhibitors, Pyrazoles pharmacology, Thiophenes pharmacology
Abstract

A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2010
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3. Bicyclic carbohydrate-derived scaffolds for combinatorial libraries.

Author

Cervi G, Peri F, Battistini C, Gennari C, and Nicotra F

Subjects
Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Bridged Bicyclo Compounds chemistry, Bridged Bicyclo Compounds pharmacology, Carbohydrate Sequence, Cell Line, Tumor, Cell Proliferation drug effects, Combinatorial Chemistry Techniques methods, Drug Screening Assays, Antitumor, Glucose chemistry, Glucose pharmacology, Humans, Male, Molecular Sequence Data, Molecular Structure, Pyrans chemistry, Antineoplastic Agents chemical synthesis, Bridged Bicyclo Compounds chemical synthesis, Colonic Neoplasms drug therapy, Glucose chemical synthesis, Prostatic Neoplasms drug therapy
Abstract

A bicyclic scaffold derived from the natural monosaccharide d-glucose, and possessing several diversity sites, was linked to various resins through the primary (C-6) hydroxyl and decorated on the solid phase: the hydroxyl group at C-4 was functionalized as ester, ether, and carbamate, the amino group in the second cycle (C-3' position) was functionalized as amide, sulfonamide, and ureido- and thioureido-derivatives. The compounds synthesized on the solid phase were tested for their antiproliferative activity on tumor cell lines.

Published
2006
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