A5085132723- Synthesis and biological activity
- Click Chemistry and Applications
- HIV/AIDS drug development and treatment
- Synthesis and Characterization of Heterocyclic Compounds
- HIV Research and Treatment
- Synthesis and Biological Evaluation
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Viral Infections and Immunology Research
- Parasites and Host Interactions
- Herpesvirus Infections and Treatments
- Biochemical and Molecular Research
- Hepatitis C virus research
- RNA and protein synthesis mechanisms
- Estrogen and related hormone effects
- Viral gastroenteritis research and epidemiology
- Receptor Mechanisms and Signaling
- Research on Leishmaniasis Studies
- Crystallization and Solubility Studies
- Viral Infections and Vectors
- X-ray Diffraction in Crystallography
- Cytomegalovirus and herpesvirus research
- Quinazolinone synthesis and applications
- Adenosine and Purinergic Signaling
- Monoclonal and Polyclonal Antibodies Research
University of Chemistry and Technology, Prague
2022-2025
Cardiff University
2015-2024
Institute of Cell Biology and Neurobiology
2020
National Research Council
2020
Sapienza University of Rome
2007-2020
Edwards (United Kingdom)
2019
King Edward VII Hospital
2017-2019
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2017
National Institutes of Health
2004-2017
University of Calabria
2015
Arylthioindoles (ATIs) that possess a 3-methoxyphenylthio or 3,5-dimethoxyphenylthio moiety at position 2 of the indole ring were effective tubulin assembly inhibitors, but weak inhibitors MCF-7 cell growth. ATIs bearing 3-(3,4,5-trimethoxyphenyl)thio potent polymerization with IC(50)s in 2.0 (35) to 4.5 (37) microM range. They also inhibited growth nanomolar concentrations. The 3,4,5-trimethoxy substituted showed potencies comparable those reference compounds colchicine and combretastatin...
Abstract SARS-CoV-2 proteases Mpro and PLpro are promising targets for antiviral drug development. In this study, we present an screening strategy involving a novel in-cell protease assay, biochemical activity assessments, as well structural determinations rapid identification of inhibitors with low cytotoxicity. We identified eight compounds anti-SARS-CoV-2 from library 64 repurposed drugs modeled at active sites by in silico docking. demonstrate that Sitagliptin Daclatasvir inhibit PLpro,...
Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and the growth MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), most potent derivative, showed IC50 = 2.0 μM, 1.6 times more active than colchicine about combretastatin A-4 (CSA4). Compound 21 inhibited cells at 13 nM. Colchicine CSA4 nM 17 values, respectively, with these
The new arylthioindole (ATI) derivatives 10, 14−18, and 21−24, which bear a halogen atom or small size ether group at position 5 of the indole moiety, were compared with reference compounds colchicine combretastatin A-4 for biological activity. Derivatives 11, 16, 21−24 inhibited MCF-7 cell growth IC50 values <50 nM. A (14−17) caused significant reduction in free energy binding compound to tubulin, concomitant cytotoxicity. In contrast, methyl (21) methoxy (22) substituents an increase...
A series of 1-aryl-5-(3',4',5'-trimethoxyphenyl) derivatives and their related 1-(3',4',5'-trimethoxyphenyl)-5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, apoptosis induction. Their activity was greater than, or comparable with, that the reference compound CA-4. Flow cytometry studies showed HeLa Jurkat cells treated with most active...
New indolylarylsulfone derivatives bearing cyclic substituents at indole-2-carboxamide linked through a methylene/ethylene spacer were potent inhibitors of the WT HIV-1 replication in CEM and PBMC cells with inhibitory concentrations low nanomolar range. Against mutant L100I K103N RT strains MT-4 cells, compounds 20, 24−26, 36, 40 showed antiviral potency superior to that NVP EFV. these strains, equipotent ETV. Molecular docking experiments on this novel series IAS analogues have also...
The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series zinc-affinic molecules explore structural requirements for selective BCA2-inhibitory An N(C═S)S—S motif required, based on activity BCA2-expressing cancer cell lines against recombinant BCA2 protein. Notably, DSF analogs (3a 3c)...
Tubulin, the major structural component of microtubules, is a target for development anticancer agents. Two series 1,5-diaryl substituted 1,2,3,4-tetrazoles were concisely synthesized, using palladium-catalyzed cross-coupling reaction, and identified as potent antiproliferative agents novel tubulin polymerization inhibitors that act at colchicine site. SAR analysis indicated compounds with 4-ethoxyphenyl group N-1 or C-5 position 1,2,3,4-tetrazole ring exhibited maximal activity. Several...
New arylthioindole derivatives having different cyclic substituents at position 2 of the indole were synthesized as anticancer agents. Several compounds inhibited tubulin polymerization submicromolar concentration and cell growth low nanomolar concentrations. Compounds 18 57 superior to previously 5. Compound was exceptionally potent an inhibitor growth: it showed IC50 = 1.0 nM in MCF-7 cells, uniformly active whole panel cancer cells colchicine combretastatin A-4. 18, 20, 55, notably more...
Dengue virus (DENV) has emerged as major human pathogen. Despite the serious socio-economic impact of DENV-associated diseases, antiviral therapy is missing. DENV replicates in cytoplasm infected cells and induces a membranous replication organelle, formed by invaginations endoplasmic reticulum membrane designated vesicle packets (VPs). Nonstructural protein 1 (NS1) multifunctional protein. It secreted from to counteract immune responses, but also critically contributes severe clinical...
Abstract In the early 1990’s a group of unrelated genes were identified from sites recurring translocations in B-cell lymphomas. Despite sharing nomenclature ‘Bcl’, and an association with blood-borne cancer, these have functions. Of genes, BCL2 is best known as key cancer target involved regulation caspases other cell viability mechanisms. BCL3 on hand was originally non-canonical regulator NF-kB transcription factor pathways – signaling mechanism associated important outcomes including...
We herein report the discovery of an entirely new category potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling terminal alkynes 5-iodo-nucleosides, are recognized for first time to be and selective inhibitors varicella-zoster virus (VZV) vitro. As structure-activity relationship we noted absolute requirement a long alkyl side chain, optimum length C(8)-C(10), activity....
Two new series of inhibitors tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized evaluated for antiproliferative activity, inhibition polymerization, cell cycle effects. Although many more derivatives have been so far, most promising compound in this was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer growth at subnanomolar concentrations interacts...
ABSTRACT Dengue viruses (DV) represent a significant global health burden, with up to 400 million infections every year and around 500,000 infected individuals developing life-threatening disease. In spite of attempts develop vaccine candidates antiviral drugs, there is lack approved therapeutics for the treatment DV infection. We have previously reported identification ST-148, small-molecule inhibitor exhibiting broad potent activity against in vitro vivo (C. M. Byrd et al., Antimicrob....
We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding colchicine tubulin, cancer cell growth. ARAP 22 showed strong P-glycoprotein-overexpressing NCI-ADR-RES Messa/Dx5MDR lines. Compounds 27 suppressed in vitro Hedgehog signaling pathway, strongly reducing...
Combretastatin A-4, a potent tubulin polymerization inhibitor, caused us to synthesize novel series of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles with the goal evaluating effects substituents on phenyl at 5-position thiazole skeleton biological activities. An ethoxy group para-position produced most active compound in series, IC(50) values 0.03-0.9 nM against five seven cancer cell lines. The compounds retained full activity multidrug resistant cells and acted through colchicine...
Two new series of inhibitors tubulin polymerization based on the 2-(alkoxycarbonyl)-3-(3′,4′,5′-trimethoxyanilino)benzo[b]thiophene and thieno[2,3-b]pyridine molecular skeletons were synthesized evaluated for antiproliferative activity a panel cancer cell lines, inhibition polymerization, cycle effects, in vivo potency. Antiproliferative was strongly dependent position methyl group benzene portion benzo[b]thiophene nucleus, with greatest observed when located at C-6 position. Also, smaller...
Prostate cancer (PC) is one of the major causes male death worldwide and development new more potent anti-PC compounds a constant requirement. Among current treatments, (R)-bicalutamide enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in case castration-resistant forms. Both these present moderate antiproliferative activity their use limited due to resistant mutants biological target. Insertion fluorinated perfluorinated groups biologically active trend...