ABSTRACT
The increasing expansion of the cities together with activities carried out on the environment by men have contributed to the deterioration of air quality. Air quality index measures how much air is free from pollution. Being aware of the healthiness of the breathed air is a right for the people. Public authorities must constantly inform the population on air quality status. Even though several pollutants are monitored by the air quality monitoring networks, providing a significant amount of data, their interpretation and presentation to the population by the public authorities is a difficult task. Some countries, for several years, have adopted evaluation procedures through daily indices that succinctly describe the air quality status in different areas of the city. The use of an index which is able to give a simple and quick information to the population represents a possible solution for the public authorities. Concerning a Mediterranean area, it has not yet been possible to adopt a single indicator to be used for informing the population. In this work, the air quality status is highlighted by the air quality index (AQI) whose purpose is to inform, in a simple and immediate way, the population. Analyzing the AQI's trend from 2013 to 2015, it was possible to assess the air quality status, obtaining an overall scenario for the purpose of protecting human health and the ecosystems. We point out that this kind of research could be applied to every region or municipality.
Subject(s)
Air Pollutants/analysis , Air Pollution/analysis , Environmental Monitoring/methods , Environmental Pollution/analysis , Cities , Humans , Mediterranean Region , Particulate Matter/analysisABSTRACT
A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a scaffold. Docking experiments showed that these molecules docked in a position and orientation similar to that of known inhibitors. Biological testing confirmed that our strategy was successful in searching for new leads as NNRTIs.
Subject(s)
Anti-HIV Agents/chemical synthesis , Benzimidazoles/chemical synthesis , HIV Reverse Transcriptase/chemistry , Reverse Transcriptase Inhibitors/chemical synthesis , Thiazoles/chemical synthesis , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Binding Sites , Crystallography, X-Ray , HIV Reverse Transcriptase/metabolism , Humans , Models, Molecular , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacologyABSTRACT
We describe the use of pharmacophore modeling as an efficient tool in the discovery of novel HIV-1 integrase (IN) inhibitors. A three-dimensional hypothetical model for the binding of diketo acid analogues to the enzyme was built by means of the Catalyst program. Using these models as a query for virtual screening, we found several compounds that contain the specified 3D patterns of chemical functions. Biological testing shows that our strategy was successful in searching for new structural leads as HIV-1 IN inhibitors.
Subject(s)
Drug Evaluation, Preclinical/statistics & numerical data , HIV Integrase Inhibitors/chemistry , HIV Integrase Inhibitors/pharmacology , Computer Simulation , DNA, Viral/drug effects , DNA, Viral/genetics , Databases, Factual , Drug Design , HIV-1/drug effects , HIV-1/enzymology , HIV-1/genetics , Models, Molecular , Molecular Structure , Structure-Activity Relationship , User-Computer InterfaceABSTRACT
Several 2,3-diaryl-1,3-thiazolidin-4-ones were synthesized and evaluated as anti-HIV agents. The results of the in vitro tests showed that some of them were highly effective inhibitors of HIV-1 replication at 30-50 nM concentrations with minimal cytotoxicity, thereby acting as non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs).
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Cell Survival/drug effects , Cell Survival/physiology , Drug Evaluation, Preclinical , HIV-1/drug effects , HIV-1/growth & development , HIV-2/drug effects , HIV-2/growth & development , Humans , Molecular Structure , Structure-Activity Relationship , T-Lymphocytes/drug effects , T-Lymphocytes/virology , Virus Replication/drug effectsABSTRACT
A model of the full-length HIV-1 integrase dimer was constructed assembling the experimentally determined structures of the single domains. Subsequently, the three-domain protein-viral DNA complex was generated for the first time through an automated docking algorithm, obtained modifying the ESCHER program, a well-known method for protein-protein docking. A detailed study of the contacts established with DNA by the enzyme revealed that the predicted model reproduced the results of mutagenesis and cross-linking experiments, confirming the validity of our docking approach in predicting the base specificity in the DNA-protein interaction.
Subject(s)
DNA, Viral/metabolism , HIV Integrase/metabolism , Base Sequence , DNA Primers , DNA, Viral/chemistry , Dimerization , Models, MolecularABSTRACT
This paper reports our work in the field of nonnucleoside RT inhibitors (NNRTIs). On the basis of extensive studies on 1H,3H-thiazolo[3,4-a]benzimidazole derivatives (TBZs) followed by structure-activity relationship (SAR) considerations and molecular modeling, the design and synthesis of a series of 2,3-diaryl-1,3-thiazolidin-4-ones have been performed. Some derivatives proved to be highly effective in inhibiting human immunodeficiency virus type-1 (HIV-1) replication at nanomolar concentrations with minimal toxicity, acting as reverse transcriptase (RT) inhibitors. Computational studies were used in order to probe the binding of our ligands to HIV-1-RT.
Subject(s)
Anti-HIV Agents/chemical synthesis , Drug Design , HIV-1/drug effects , HIV-1/enzymology , Reverse Transcriptase Inhibitors/chemical synthesis , Animals , Anti-HIV Agents/metabolism , Anti-HIV Agents/pharmacology , Humans , Reverse Transcriptase Inhibitors/metabolism , Reverse Transcriptase Inhibitors/pharmacology , Structure-Activity Relationship , Technology, Pharmaceutical/methodsABSTRACT
Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a variously substituted phenyl ring at N-3 have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Cell Line , HIV-1/drug effects , HIV-1/growth & development , HIV-2/drug effects , HIV-2/growth & development , Humans , Virus Replication/drug effectsABSTRACT
The synthesis of 1,2-substituted benzimidazoles is reported. These novel derivatives share chemical similarities with 1-aryl-1H,3H-thiazolo[3,4-a]benzimidazoles, a class of HIV-1 NNRTIs studied widely. All compounds prepared were tested in MT-4 cells to explore their potential anti-HIV activity and were found to be less potent than 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TBZ).
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Cell Line, Transformed , HIV-1/drug effects , HIV-2/drug effects , Humans , Lethal Dose 50 , Models, Molecular , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacology , Structure-Activity Relationship , Virus Replication/drug effectsABSTRACT
Starting from 1H,3H-thiazolo[3,4-a]benzimidazoles (TBZs), we performed the design, synthesis, and the structure-activity relationship studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations with minimal cytotoxicity, thereby acting as nonnucleoside HIV-1 RT inhibitors (NNRTIs). Computational studies were used to delineate the ligand-RT interactions and to probe the binding of the ligands to HIV-1 RT.
Subject(s)
Anti-HIV Agents/chemical synthesis , Reverse Transcriptase Inhibitors/chemical synthesis , Thiazoles/chemical synthesis , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Cell Line , Drug Design , HIV Reverse Transcriptase/antagonists & inhibitors , HIV Reverse Transcriptase/chemistry , HIV-1/drug effects , Humans , Ligands , Models, Molecular , Protein Binding , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Structure-Activity Relationship , Thiazoles/chemistry , Thiazoles/pharmacology , Virus ReplicationABSTRACT
Several 2,3-diaryl-1,3-thiazolidine-4-thione derivatives and 2,3-diaryl-1,3-thiazolidin-4-ones bearing a methyl group at C-5 position have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.
