Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction
The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After devel...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
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| Series: | Results in Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715623004046 |
| _version_ | 1827591217319247872 |
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| author | Maria Francesca Armentano Paolo Lupattelli Faustino Bisaccia Rosarita D'Orsi Rocchina Miglionico Ilaria Nigro Alessandro Santarsiere Federico Berti Maria Funicello Lucia Chiummiento |
| author_facet | Maria Francesca Armentano Paolo Lupattelli Faustino Bisaccia Rosarita D'Orsi Rocchina Miglionico Ilaria Nigro Alessandro Santarsiere Federico Berti Maria Funicello Lucia Chiummiento |
| author_sort | Maria Francesca Armentano |
| collection | DOAJ |
| description | The Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. Absorption, distribution, metabolism, excretion (ADME) properties were also evaluated in silico, showing the potential of such compounds to be developed as drugs. |
| first_indexed | 2024-03-09T01:28:41Z |
| format | Article |
| id | doaj.art-cd30dfc7f8ac4c1e85f277fe1e057030 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-09T01:28:41Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-cd30dfc7f8ac4c1e85f277fe1e0570302023-12-10T06:15:28ZengElsevierResults in Chemistry2211-71562023-12-016101165Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME predictionMaria Francesca Armentano0Paolo Lupattelli1Faustino Bisaccia2Rosarita D'Orsi3Rocchina Miglionico4Ilaria Nigro5Alessandro Santarsiere6Federico Berti7Maria Funicello8Lucia Chiummiento9Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyDipartimento di Chimica, Università “La Sapienza” di Roma, Piazzale A. Moro 4, Roma ItalyDipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyDipartimento di Chimica e Chimica Industriale (DCCI), Università di Pisa, Via G. Moruzzi 13I, 56124 Pisa, ItalyDipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyDipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyDipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyDipartimento di Scienze Chimiche e Farmaceutiche, Università di Trieste, Via Giorgieri 1, 34127 Trieste, Italy; Corresponding authors.Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy; Corresponding authors.Dipartimento di Scienze, Università della Basilicata, Via Ateneo Lucano 10, 85100 Potenza, ItalyThe Virus HIV-1 infection still represents a serious disease even if actually it is transformed in chronic pathology. Considering the crucial role of the enzyme Protease in life cycle of HIV many efforts have been made in the research of new organic compounds showing inhibitory activity. After development of several series of non peptidic inhibitors we report here the synthesis of novel simple HIV-Protease inhibitors containing heteroaryl carboxamides and their antiviral activity in vitro and in HEK293 cells. Benzofuryl- benzothienyl- and indolyl rings as well as aryl sulfonamides with different electronic properties have been introduced by efficient synthetic procedures. All compounds showed inhibitory activity similar to the commercial drug Darunavir, effective against both wild-type HIV-1 protease and that containing the V32I or V82A mutations. Absorption, distribution, metabolism, excretion (ADME) properties were also evaluated in silico, showing the potential of such compounds to be developed as drugs.http://www.sciencedirect.com/science/article/pii/S2211715623004046Mutate HIV protease inhibitorsCarboxamidesHeteroarenesMammalian cells essayADME |
| spellingShingle | Maria Francesca Armentano Paolo Lupattelli Faustino Bisaccia Rosarita D'Orsi Rocchina Miglionico Ilaria Nigro Alessandro Santarsiere Federico Berti Maria Funicello Lucia Chiummiento Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction Results in Chemistry Mutate HIV protease inhibitors Carboxamides Heteroarenes Mammalian cells essay ADME |
| title | Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction |
| title_full | Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction |
| title_fullStr | Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction |
| title_full_unstemmed | Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction |
| title_short | Novel wild type and mutate HIV-1 protease inhibitors containing heteroaryl carboxamides in P2: Synthesis, biological evaluations and in silico ADME prediction |
| title_sort | novel wild type and mutate hiv 1 protease inhibitors containing heteroaryl carboxamides in p2 synthesis biological evaluations and in silico adme prediction |
| topic | Mutate HIV protease inhibitors Carboxamides Heteroarenes Mammalian cells essay ADME |
| url | http://www.sciencedirect.com/science/article/pii/S2211715623004046 |
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