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Your search keyword '"FUNICELLO, M."' showing total 3 results
Start Over Author "FUNICELLO, M." Journal bioorganic medicinal chemistry
3 results on '"FUNICELLO, M."'

1. New heteroaryl carbamates: Synthesis and biological screening in vitro and in mammalian cells of wild-type and mutant HIV-protease inhibitors.

Author

Tramutola F, Armentano MF, Berti F, Chiummiento L, Lupattelli P, D'Orsi R, Miglionico R, Milella L, Bisaccia F, and Funicello M

Subjects
Binding Sites, Carbamates pharmacology, Catalytic Domain, Drug Resistance, Neoplasm drug effects, HEK293 Cells, HIV Protease metabolism, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, Humans, Molecular Docking Simulation, Mutation, Carbamates chemistry, HIV Protease genetics, HIV Protease Inhibitors chemical synthesis
Abstract

New heteroaryl HIV-protease inhibitors bearing a carbamoyl spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core that can have either H or benzyl group. The in vitro inhibition activity against recombinant protease showed a general beneficial effect of both carbamoyl moiety and the benzyl group, ranging the IC 50 values between 11 and 0.6 nM. In particular, benzofuryl and indolyl derivatives showed IC 50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such derivatives in terms of number of interactions in the active site, supporting the experimental results. The inhibition activity was also confirmed in HEK293 mammalian cells and was maintained against protease mutants. Furthermore, the metabolic stability was comparable with that of the commercially available inhibitors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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2. Synthesis and biological evaluation in vitro and in mammalian cells of new heteroaryl carboxyamides as HIV-protease inhibitors.

Author

Funicello M, Chiummiento L, Tramutola F, Armentano MF, Bisaccia F, Miglionico R, Milella L, Benedetti F, Berti F, and Lupattelli P

Subjects
Amides chemical synthesis, Amides pharmacology, Binding Sites, Cell Survival drug effects, HEK293 Cells, HIV drug effects, HIV enzymology, HIV Protease chemistry, HIV Protease Inhibitors pharmacology, Humans, Inhibitory Concentration 50, Microscopy, Fluorescence, Molecular Docking Simulation, Protein Structure, Tertiary, Structure-Activity Relationship, Transfection, Amides chemistry, HIV Protease metabolism, HIV Protease Inhibitors chemical synthesis
Abstract

New heteroaryl HIV-protease inhibitors bearing a carboxyamide spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core modifying the type of heteroarene and the central core, with the presence of either H or benzyl group. Their in vitro inhibition activity against recombinant protease showed a general beneficial effect of carboxyamide moiety, the IC 50 values ranging between 1 and 15nM. In particular benzofuryl derivatives showed IC 50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such benzofuryl derivatives in terms of number of interactions in the active site, supporting the experimental results on activity. The inhibition activity of such molecules has been also evaluated in HEK293 cells expressing the protease fused to green fluorescent protein, by western blotting analysis, fluorescence microscopy and cytofluorimetry., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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3. Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: the effect of different substitution patterns.

Author

Bonini C, Chiummiento L, Di Blasio N, Funicello M, Lupattelli P, Tramutola F, Berti F, Ostric A, Miertus S, Frecer V, and Kong DX

Subjects
Dose-Response Relationship, Drug, HIV Protease Inhibitors chemical synthesis, Indoles chemical synthesis, Models, Molecular, Molecular Structure, Peptides, Structure-Activity Relationship, HIV Protease metabolism, HIV Protease Inhibitors chemistry, HIV Protease Inhibitors pharmacology, Indoles chemistry, Indoles pharmacology
Abstract

New structurally simple indolic non peptidic HIV Protease inhibitors were synthesized from (S)-glycidol by regioselective methods. Following the concept of targeting the protein backbone, different substitution patterns were introduced onto the common stereodefined isopropanolamine core modifying the type of functional group on the indole, the position of the functional group on the indole and the type of the nitrogen containing group (sulfonamides or perhydroisoquinoline), alternatively. The systematic study on in vitro inhibition activity of such compounds confirmed the general beneficial effect of the 5-indolyl substituents in presence of arylsulfonamide moieties, which furnished activities in the micromolar range. Preliminary docking analysis allowed to identify several key features of the binding mode of such compounds to the protease., (Copyright © 2014. Published by Elsevier Ltd.)

Published
2014
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