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Your search keyword '"FUNICELLO, M."' showing total 7 results
Start Over Author "FUNICELLO, M." Topic hiv protease
7 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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4. Synthesis of new thienyl ring containing HIV-1 protease inhibitors: promising preliminary pharmacological evaluation against recombinant HIV-1 proteases.

Author

Bonini C, Chiummiento L, De Bonis M, Di Blasio N, Funicello M, Lupattelli P, Pandolfo R, Tramutola F, and Berti F

Subjects
Asparagine chemical synthesis, Asparagine chemistry, HIV Protease genetics, HIV Protease Inhibitors chemistry, Mutation, Nelfinavir chemistry, Quinolines chemistry, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins chemistry, Saquinavir chemistry, Stereoisomerism, Structure-Activity Relationship, Asparagine analogs & derivatives, HIV Protease chemistry, HIV Protease Inhibitors chemical synthesis, Nelfinavir analogs & derivatives, Nelfinavir chemical synthesis, Quinolines chemical synthesis, Saquinavir analogs & derivatives, Saquinavir chemical synthesis
Abstract

A series of new thienyl ring containing analogues of nelfinavir and saquinavir with different substitution patterns were synthesized from suitable enantiopure diols. Their inhibitory activity against wild type recombinant HIV-1 protease was evaluated. In general thienyl groups spaced from the core by a methylene group gave products showing IC(50) in the nanomolar range, irrespective of the type and the substitution pattern of the heterocycle. The range of activity of the two most active compounds is substantially maintained or even increased against two commonly selected mutants, under drug pressure, such as V32I and V82A.

Published
2010
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5. Synthesis and biological evaluation in vitro and in mammalian cells of new heteroaryl carboxyamides as HIV-protease inhibitors

Author

Luigi Milella, Maria Funicello, Federico Berti, Fabio Benedetti, Paolo Lupattelli, Faustino Bisaccia, Francesco Tramutola, Lucia Chiummiento, Maria Francesca Armentano, Rocchina Miglionico, Funicello, M., Chiummiento, L., Tramutola, F., Armentano, M. F., Bisaccia, F., Miglionico, R., Milella, L., Benedetti, F., Berti, F., and Lupattelli, P.

Subjects
0301 basic medicine, Amide, medicine.medical_treatment, Clinical Biochemistry, Pharmaceutical Science, 01 natural sciences, Biochemistry, chemistry.chemical_compound, HEK293 Cell, HIV Protease, Drug Discovery, Moiety, HIV Protease Inhibitor, Microscopy, biology, Molecular Docking Simulation, Benzyl group, Molecular Medicine, Human, Protein Structure, Stereochemistry, Cell Survival, Transfection, Fluorescence, 03 medical and health sciences, Inhibitory Concentration 50, Structure-Activity Relationship, medicine, Structure–activity relationship, Humans, Molecular Biology, Protease, Binding Sites, 010405 organic chemistry, Organic Chemistry, Binding Site, Active site, HIV, HIV Protease Inhibitors, Amides, In vitro, 0104 chemical sciences, Protein Structure, Tertiary, 030104 developmental biology, HEK293 Cells, chemistry, Microscopy, Fluorescence, Docking (molecular), biology.protein, Tertiary
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 cen- tral core, with the presence of either H or benzyl group. Their in vitro inhibition activity against recom- binant protease showed a general beneficial effect of carboxyamide moiety, the IC50 values ranging between 1 and 15 nM. In particular benzofuryl derivatives showed IC50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such benzo- furyl 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 pro- tease fused to green fluorescent protein, by western blotting analysis, fluorescence microscopy and cytofluorimetry.

Published
2017

6. Synthesis and biological evaluation of new simple indolic non peptidic HIV Protease inhibitors: The effect of different substitution patterns

Author

Paolo Lupattelli, D. X. Kong, Adrian Ostric, Stanislav Miertus, Lucia Chiummiento, Vladimir Frecer, Maria Funicello, Carlo Bonini, N. Di Blasio, Federico Berti, Francesco Tramutola, Bonini, C, Chiummiento, L., Di Blasio, N., Funicello, M., Lupattelli, P., Tramutola, F., Berti, Federico, Ostric, Adrian, Miertus, S., Frecer, V., and Kong, D. X.

Subjects
Models, Molecular, Indoles, Stereochemistry, medicine.medical_treatment, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Dose-Response Relationship, Structure-Activity Relationship, HIV PR inhibitors, Non-peptidic inhibitors, Dose-Response Relationship, Drug, HIV Protease, HIV Protease Inhibitors, Drug Discovery, medicine, HIV Protease Inhibitor, Peptide bond, Molecular Biology, Biological evaluation, Indole test, HIV PR inhibitor, Protease, Molecular Structure, Chemistry, Organic Chemistry, Regioselectivity, In vitro, Docking (molecular), Indole, Molecular Medicine, Non-peptidic inhibitor, Drug, Peptides
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.

Published
2014

7. Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containign hydroxyethylamino core

Author

Carlo Bonini, Gerardina Suanno, Margherita De Bonis, Federico Berti, Maria Funicello, Lucia Chiummiento, Paolo Lupattelli, Pietro Campaner, Bonini, C., Chiummiento, L., DE BONIS, M., Funicello, M., Lupattelli, P., Suanno, G., Berti, Federico, and Campaner, Pietro

Subjects
Acrylate, Stereochemistry, Peptidomimetic, Organic Chemistry, Regioselectivity, HIV protease, peptidomimetics, stereoselectivity, Biological activity, Alcohol, biochemical phenomena, metabolism, and nutrition, Biochemistry, peptidomimetic, chemistry.chemical_compound, chemistry, Drug Discovery, Thiophene, Sodium azide, Sharpless asymmetric dihydroxylation
Abstract

An efficient method has been developed for the synthesis of a versatile intermediate bearing azido, hydroxyl and ester functions, a useful precursor for peptidomimetic compounds. The two main features for this synthesis were the use of the Sharpless asymmetric dihydroxylation on thiophene acrylate and the subsequent regioselective ring opening by sodium azide of the cyclic sulfite. Highly chemoselective reduction of the azido alcohol led to a key compound which was utilized for the synthesis of two analogues of commercial anti HIV PR such as nelfinavir and saquinavir. The biological activity and molecular modelling study on these two new potential drugs have been evaluated.

Published
2005

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