LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 94

Search options

  1. Article ; Online: Techniques and Strategies in Drug Design and Discovery.

    Nitulescu, George Mihai

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: The process of drug discovery constitutes a highly intricate and formidable undertaking, encompassing the identification and advancement of novel therapeutic entities [ ... ]. ...

    Abstract The process of drug discovery constitutes a highly intricate and formidable undertaking, encompassing the identification and advancement of novel therapeutic entities [...].
    MeSH term(s) Drug Design ; Drug Discovery
    Language English
    Publishing date 2024-01-23
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031364
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents.

    Nitulescu, George Mihai

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 10

    Abstract: The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute ...

    Abstract The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI's panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds' averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis-Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect's potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates.
    MeSH term(s) Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Pyrazoles/chemistry ; Pyrazoles/pharmacology
    Chemical Substances Antineoplastic Agents ; Pyrazoles
    Language English
    Publishing date 2022-05-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27103300
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: A PIM-1 Kinase Inhibitor Docking Optimization Study Based on Logistic Regression Models and Interaction Analysis.

    Ion, George Nicolae Daniel / Nitulescu, George Mihai / Mihai, Dragos Paul

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 8

    Abstract: PIM-1 kinase is a serine-threonine phosphorylating enzyme with implications in multiple types of malignancies, including prostate, breast, and blood cancers. Developing better search methodologies for PIM-1 kinase inhibitors may be a good strategy to ... ...

    Abstract PIM-1 kinase is a serine-threonine phosphorylating enzyme with implications in multiple types of malignancies, including prostate, breast, and blood cancers. Developing better search methodologies for PIM-1 kinase inhibitors may be a good strategy to speed up the discovery of an oncological drug approved for targeting this specific kinase. Computer-aided screening methods are promising approaches for the discovery of novel therapeutics, although certain limitations should be addressed. A frequent omission that is encountered in molecular docking is the lack of proper implementation of scoring functions and algorithms on the post-docking results, which usually alters the outcome of the virtual screening. The current study suggests a method for post-processing docking results, expressed either as binding affinity or score, that considers different binding modes of known inhibitors to the studied targets while making use of in vitro data, where available. The docking protocol successfully discriminated between known PIM-1 kinase inhibitors and decoy molecules, although binding energies alone were not sufficient to ensure a successful prediction. Logistic regression models were trained to predict the probability of PIM-1 kinase inhibitory activity based on binding energies and the presence of interactions with identified key amino acid residues. The selected model showed 80.9% true positive and 81.4% true negative rates. The discussed approach can be further applied in large-scale molecular docking campaigns to increase hit discovery success rates.
    Language English
    Publishing date 2023-07-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13081635
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Quantitative and Qualitative Analysis of the Anti-Proliferative Potential of the Pyrazole Scaffold in the Design of Anticancer Agents

    George Mihai Nitulescu

    Molecules, Vol 27, Iss 3300, p

    2022  Volume 3300

    Abstract: The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute ...

    Abstract The current work presents an objective overview of the impact of one important heterocyclic structure, the pyrazole ring, in the development of anti-proliferative drugs. A set of 1551 pyrazole derivatives were extracted from the National Cancer Institute (NCI) database, together with their growth inhibition effects (GI%) on the NCI’s panel of 60 cancer cell lines. The structures of these derivatives were analyzed based on the compounds’ averages of GI% values across NCI-60 cell lines and the averages of the values for the outlier cells. The distribution and the architecture of the Bemis–Murcko skeletons were analyzed, highlighting the impact of certain scaffold structures on the anti-proliferative effect’s potency and selectivity. The drug-likeness, chemical reactivity and promiscuity risks of the compounds were predicted using AMDETlab. The pyrazole ring proved to be a versatile scaffold for the design of anticancer drugs if properly substituted and if connected with other cyclic structures. The 1,3-diphenyl-pyrazole emerged as a useful scaffold for potent and targeted anticancer candidates.
    Keywords anti-proliferative ; privileged scaffold ; pyrazole ; indazole ; pyrazolopyrimidine ; pyrazolotriazine ; Organic chemistry ; QD241-441
    Subject code 540
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article: Discovery of New Microbial Collagenase Inhibitors.

    Nitulescu, Georgiana / Mihai, Dragos Paul / Zanfirescu, Anca / Stan, Miruna Silvia / Gradinaru, Daniela / Nitulescu, George Mihai

    Life (Basel, Switzerland)

    2022  Volume 12, Issue 12

    Abstract: Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such ... ...

    Abstract Bacterial virulence factors are mediating bacterial pathogenesis and infectivity. Collagenases are virulence factors secreted by several bacterial stains, such as
    Language English
    Publishing date 2022-12-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life12122114
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article: Resveratrol and Other Natural Oligomeric Stilbenoid Compounds and Their Therapeutic Applications.

    Duta-Bratu, Cosmina-Gabriela / Nitulescu, George Mihai / Mihai, Dragos Paul / Olaru, Octavian Tudorel

    Plants (Basel, Switzerland)

    2023  Volume 12, Issue 16

    Abstract: The use of natural compounds as an alternative to synthetic molecules has become a significant subject of interest in recent decades. Stilbenoids are a group of phenolic compounds found in many plant species and they have recently gained the focus of a ... ...

    Abstract The use of natural compounds as an alternative to synthetic molecules has become a significant subject of interest in recent decades. Stilbenoids are a group of phenolic compounds found in many plant species and they have recently gained the focus of a multitude of studies in medicine and chemistry, resveratrol being the most representative molecule. In this review, we focused on the research that illustrates the therapeutic potential of this class of natural molecules considering various diseases with higher incidence rates. PubChem database was searched for bioactivities of natural stilbenoids, while several keywords (i.e., "stilbenoids", "stilbenoid anticancer") were used to query PubMed database for relevant studies. The diversity and the simplicity of stilbenes' chemical structures together with the numerous biological sources are key elements that can simplify both the isolation of these compounds and the drug design of novel bioactive molecules. Resveratrol and other related compounds are heterogeneously distributed in plants and are mainly found in grapes and wine. Natural stilbenes were shown to possess a wide range of biological activities, such as antioxidant, anti-inflammatory, antihyperglycemic, cardioprotective, neuroprotective, and antineoplastic properties. While resveratrol is widely investigated for its benefits in various disorders, further studies are warranted to properly harness the therapeutic potential of less popular stilbenoid compounds.
    Language English
    Publishing date 2023-08-14
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2704341-1
    ISSN 2223-7747
    ISSN 2223-7747
    DOI 10.3390/plants12162935
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article: Identifying FAAH Inhibitors as New Therapeutic Options for the Treatment of Chronic Pain through Drug Repurposing.

    Zanfirescu, Anca / Nitulescu, Georgiana / Mihai, Dragos Paul / Nitulescu, George Mihai

    Pharmaceuticals (Basel, Switzerland)

    2021  Volume 15, Issue 1

    Abstract: Chronic pain determines a substantial burden on individuals, employers, healthcare systems, and society. Most of the affected patients report dissatisfaction with currently available treatments. There are only a few and poor therapeutic options-some ... ...

    Abstract Chronic pain determines a substantial burden on individuals, employers, healthcare systems, and society. Most of the affected patients report dissatisfaction with currently available treatments. There are only a few and poor therapeutic options-some therapeutic agents are an outgrowth of drugs targeting acute pain, while others have several serious side effects. One of the primary degradative enzymes for endocannabinoids, fatty acid amide hydrolase (FAAH) attracted attention as a significant molecular target for developing new therapies for neuropsychiatric and neurological diseases, including chronic pain. Using chemical graph mining, quantitative structure-activity relationship (QSAR) modeling, and molecular docking techniques we developed a multi-step screening protocol to identify repurposable drugs as FAAH inhibitors. After screening the DrugBank database using our protocol, 273 structures were selected, with five already approved drugs, montelukast, repaglinide, revefenacin, raloxifene, and buclizine emerging as the most promising repurposable agents for treating chronic pain. Molecular docking studies indicated that the selected compounds interact with the enzyme mostly non-covalently (except for revefenacin) through shape complementarity to the large substrate-binding pocket in the active site. A molecular dynamics simulation was employed for montelukast and revealed stable interactions with the enzyme. The biological activity of the selected compounds should be further confirmed by employing in vitro and in vivo studies.
    Language English
    Publishing date 2021-12-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2193542-7
    ISSN 1424-8247
    ISSN 1424-8247
    DOI 10.3390/ph15010038
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Identifying FAAH Inhibitors as New Therapeutic Options for the Treatment of Chronic Pain through Drug Repurposing

    Anca Zanfirescu / Georgiana Nitulescu / Dragos Paul Mihai / George Mihai Nitulescu

    Pharmaceuticals, Vol 15, Iss 38, p

    2022  Volume 38

    Abstract: Chronic pain determines a substantial burden on individuals, employers, healthcare systems, and society. Most of the affected patients report dissatisfaction with currently available treatments. There are only a few and poor therapeutic options—some ... ...

    Abstract Chronic pain determines a substantial burden on individuals, employers, healthcare systems, and society. Most of the affected patients report dissatisfaction with currently available treatments. There are only a few and poor therapeutic options—some therapeutic agents are an outgrowth of drugs targeting acute pain, while others have several serious side effects. One of the primary degradative enzymes for endocannabinoids, fatty acid amide hydrolase (FAAH) attracted attention as a significant molecular target for developing new therapies for neuropsychiatric and neurological diseases, including chronic pain. Using chemical graph mining, quantitative structure–activity relationship (QSAR) modeling, and molecular docking techniques we developed a multi-step screening protocol to identify repurposable drugs as FAAH inhibitors. After screening the DrugBank database using our protocol, 273 structures were selected, with five already approved drugs, montelukast, repaglinide, revefenacin, raloxifene, and buclizine emerging as the most promising repurposable agents for treating chronic pain. Molecular docking studies indicated that the selected compounds interact with the enzyme mostly non-covalently (except for revefenacin) through shape complementarity to the large substrate-binding pocket in the active site. A molecular dynamics simulation was employed for montelukast and revealed stable interactions with the enzyme. The biological activity of the selected compounds should be further confirmed by employing in vitro and in vivo studies.
    Keywords endocannabinoids ; chronic pain ; N-arachidonoylethanolamide ; fatty acid amide hydrolase ; drug repurposing ; montelukast ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 540
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  9. Article ; Online: The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.

    Nitulescu, George Mihai / Stancov, Gheorghe / Seremet, Oana Cristina / Nitulescu, Georgiana / Mihai, Dragos Paul / Duta-Bratu, Cosmina Gabriela / Barbuceanu, Stefania Felicia / Olaru, Octavian Tudorel

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 14

    Abstract: The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases inhibitors (PKI) is the best available option for the cure of cancer. The pyrazole ... ...

    Abstract The altered activation or overexpression of protein kinases (PKs) is a major subject of research in oncology and their inhibition using small molecules, protein kinases inhibitors (PKI) is the best available option for the cure of cancer. The pyrazole ring is extensively employed in the field of medicinal chemistry and drug development strategies, playing a vital role as a fundamental framework in the structure of various PKIs. This scaffold holds major importance and is considered a privileged structure based on its synthetic accessibility, drug-like properties, and its versatile bioisosteric replacement function. It has proven to play a key role in many PKI, such as the inhibitors of Akt, Aurora kinases, MAPK, B-raf, JAK, Bcr-Abl, c-Met, PDGFR, FGFRT, and RET. Of the 74 small molecule PKI approved by the US FDA, 8 contain a pyrazole ring: Avapritinib, Asciminib, Crizotinib, Encorafenib, Erdafitinib, Pralsetinib, Pirtobrutinib, and Ruxolitinib. The focus of this review is on the importance of the unfused pyrazole ring within the clinically tested PKI and on the additional required elements of their chemical structures. Related important pyrazole fused scaffolds like indazole, pyrrolo[1,2-b]pyrazole, pyrazolo[4,3-b]pyridine, pyrazolo[1,5-a]pyrimidine, or pyrazolo[3,4-d]pyrimidine are beyond the subject of this work.
    MeSH term(s) Pyrazoles/chemistry ; Pyrazoles/pharmacology ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/classification ; Protein Kinase Inhibitors/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Drug Design ; Structure-Activity Relationship ; Humans ; Animals
    Chemical Substances Pyrazoles ; pyrazole (3QD5KJZ7ZJ) ; Protein Kinase Inhibitors ; Antineoplastic Agents
    Language English
    Publishing date 2023-07-12
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28145359
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article: Candidates for Repurposing as Anti-Virulence Agents Based on the Structural Profile Analysis of Microbial Collagenase Inhibitors.

    Nitulescu, Georgiana / Nitulescu, George Mihai / Zanfirescu, Anca / Mihai, Dragos Paul / Gradinaru, Daniela

    Pharmaceutics

    2021  Volume 14, Issue 1

    Abstract: The pharmacological inhibition of the bacterial collagenases (BC) enzymes is considered a promising strategy to block the virulence of the bacteria without targeting the selection mechanism leading to drug resistance. The chemical structures of ... ...

    Abstract The pharmacological inhibition of the bacterial collagenases (BC) enzymes is considered a promising strategy to block the virulence of the bacteria without targeting the selection mechanism leading to drug resistance. The chemical structures of the
    Language English
    Publishing date 2021-12-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics14010062
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top