Phenylthiazoles with potent & optimum selectivity toward .

() is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires urgent and aggressive action. Interruption of the human gut microbiome and the development of antibiotic resistance urgently require development and synthesis of effective alternative antibiotics with minimal effects on the normal gut microbial flora. In this study, cyclization of the aminoguanidine head to the thiazole nucleus while maintaining its other pharmacophoric features leads to selective targeting of as shown in the graphical abstract.

New thiazolidine-2,4-diones as potential anticancer agents and apoptotic inducers targeting VEGFR-2 kinase: Design, synthesis, in silico and in vitro studies.

Background: VEGFR-2 has emerged as a prominent positive regulator of cancer progression.

Aim: Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2.

Methods: Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay.

Discovery of new thiazolidine-2,4-dione derivatives as potential VEGFR-2 inhibitors: and studies.

In this study, a series of seven novel 2,4-dioxothiazolidine derivatives with potential anticancer and VEGFR-2 inhibiting abilities were designed and synthesized as VEGFR-2 inhibitors. The synthesized compounds were tested for their potential to inhibit VEGFR-2 and the growth of HepG2 and MCF-7 cancer cell lines. Among the compounds tested, compound (IC = 0.

Novel phenylthiazoles with a -butyl moiety: promising antimicrobial activity against multidrug-resistant pathogens with enhanced ADME properties.

The structure-activity relationship of a new -butylphenylthiazole series, with a pyrimidine linker, was investigated. We wished to expand knowledge of this novel class of antibiotics by generating 21 new derivatives bearing ≥2 heteroatoms in their side chains. Their activity was examined against isolates of methicillin-resistant (MRSA), , , , and .

Discovery of new VEGFR-2 inhibitors and apoptosis inducer-based thieno[2,3-]pyrimidine.

VEGFR-2 is a key regulator of cancer cell proliferation, migration and angiogenesis. Development of thieno[2,3-]pyrimidine derivatives as potential anti-cancer agents targeting VEGFR-2. Seven and nine studies were conducted.

Virtual screening approach for the discovery of selective 5α-reductase type II inhibitors for benign prostatic hyperplasia treatment.

5α-Reductase type II (5αR2) inhibition is a promising strategy for benign prostatic hyperplasia treatment. A computational approach including virtual screening, ligand-based 3D pharmacophore modeling, 2D quantitative structure-activity relationship and molecular docking simulations were adopted to develop novel inhibitors. Hits were first filtered via the validated pharmacophore and 2D quantitative structure-activity relationship models.

Naphthylthiazoles: a class of broad-spectrum antifungals.

Cryptococcal infections remain a major cause of mortality worldwide due to the ability of to pass through the blood-brain barrier (BBB) causing lethal meningitis. The limited number of available therapeutics, which exhibit limited availability, severe toxicity and low tolerability, necessitates the development of new therapeutics. Investigating the antifungal activity of a novel series of naphthylthiazoles provided -diaminocyclohexyl derivative 18 with many advantageous attributes as a potential therapeutic for cryptococcal meningitis.

Design, synthesis, anti-proliferative evaluation, docking, and MD simulation studies of new thieno[2,3-]pyrimidines targeting VEGFR-2.

In this work, new thieno[2,3-]pyrimidine-derived compounds possessing potential anticancer activities were designed and synthesized to target VEGFR-2. The thieno[2,3-]pyrimidine derivatives were tested for their abilities to inhibit VEGFR-2 and to prevent cancer cell growth in two types of cancer cells, MCF-7 and HepG2. Compound 18 exhibited the strongest anti-VEGFR-2 potential with an IC value of 0.

Discovery of New Uracil and Thiouracil Derivatives as Potential HDAC Inhibitors.

: Histone deacetylase inhibitors (HDACIs) are a relatively new class of potential drugs for treating cancer. : Discovery of new anticancer agents targeting HDAC. : New uracil and thiouracil derivatives panels were designed and synthesized as HDAC inhibitors.

New thiouracil derivatives as histone deacetylase inhibitors and apoptosis inducers: design, synthesis and anticancer evaluation.

Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. To introduce new active HDAC inhibitors. Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation.

Development of pyrolo[2,3-c]pyrazole, pyrolo[2,3-d]pyrimidine and their bioisosteres as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological evaluation and molecular dynamics investigations.

Inhibiting the CDK2/cyclin A2 enzyme has been validated in multiple clinical manifestations related to multiple types of cancer. Herein, novel series of pyrolo[2,3-c]pyrazole, pyrolo[2,3-c]isoaxazole and pyrolo[2,3-d]pyrimidine, pyrolo[3,2-c]pyridine & indole based analogs were designed, synthesized and biologically evaluated for their in vitro antiproliferative activity where the obtained results revealed that most of the newly synthesized compounds showed significant cytotoxic activity towards MCF-7 (breast cancer cell lines) and HepG-2 (hepatocellular carcinoma) with IC ranging from 3.20 µM to 10.

Exploring novel aryl/heteroaryl-isosteres of phenylthiazole against multidrug-resistant bacteria.

Antimicrobial resistance has become a concern as a worldwide threat. A novel scaffold of phenylthiazoles was recently evaluated against multidrug-resistant to control the emergence and spread of antimicrobial resistance, showing good results. Several structural modifications are needed based on the structure-activity relationships (SARs) of this new antibiotic class.

New indole derivatives as multitarget anti-Alzheimer's agents: synthesis, biological evaluation and molecular dynamics.

Alzheimer's disease is a neurological disorder that causes brain cells to shrink and die. Thirteen novel 'oxathiolanyl', 'pyrazolyl' and 'pyrimidinyl' indole derivatives were designed and synthesized as anti-Alzheimer's disease treatment. enzyme assay was performed against both AChE and BChE enzymes.

Design, synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers.

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives ( and ) were selected for IC screening.

Synthesis, biological evaluation, and studies of new CDK2 inhibitors based on pyrazolo[3,4-]pyrimidine and pyrazolo[4,3-][1,2,4]triazolo[1,5-]pyrimidine scaffold with apoptotic activity.

Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives () was designed and synthesised as novel CDK2 inhibitors.

Discovery of pyrazolo[3,4-]pyrimidine and pyrazolo[4,3-][1,2,4]triazolo[1,5-]pyrimidine derivatives as novel CDK2 inhibitors: synthesis, biological and molecular modeling investigations.

CDK2 inhibition is an appealing target for cancer treatment that targets tumor cells in a selective manner. A new set of small molecules featuring the privileged pyrazolo[3,4-]pyrimidine and pyrazolo[4,3-][1,2,4]triazolo[1,5-]pyrimidine scaffolds (4-13) as well as the thioglycoside derivatives (14, 15) were designed, and synthesized as novel CDK2 targeting compounds. The growth of the three examined cell lines was significantly inhibited by most of the prepared compounds.

Design, synthesis, docking study and anticancer evaluation of new trimethoxyphenyl pyridine derivatives as tubulin inhibitors and apoptosis inducers.

Microtubules have become an appealing target for anticancer drug development including mainly colchicine binding site inhibitors (CBSIs). A new series of novel trimethoxypyridine derivatives were designed and synthesized as tubulin targeting agents. anti-proliferative activities of the tested compounds compared to colchicine against hepatocellular carcinoma (HepG-2), colorectal carcinoma (HCT-116), and breast cancer (MCF-7) was carried out.

1,3,4-Oxadiazole-naphthalene hybrids as potential VEGFR-2 inhibitors: design, synthesis, antiproliferative activity, apoptotic effect, and studies.

In the current work, some 1,3,4-oxadiazole-naphthalene hybrids were designed and synthesised as VEGFR-2 inhibitors. The synthesised compounds were evaluated for their antiproliferative activity against two human cancer cell lines namely, HepG-2 and MCF-7. Compounds that exhibited promising cytotoxicity (, , , , , and ) were further evaluated for their VEGFR-2 inhibitory activities.

Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1'-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17).

Design, Synthesis, biological Evaluation, and molecular docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers.

A series of novel hybrid pyrazolo[3,4-d]pyramidine derivatives was designed and chemically synthesized in useful yields. The synthesized compounds were structurally characterized by the usual techniques. All the new synthesized compounds were biologically screened in vitro for their antiproliferative activities against a panel of four cancer cell lines, namely HepG-2, MCF-7, HCT-116, and Hela.

Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation.

Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin polymerisation agents. Thus, new quinoline derivatives have been designed and synthesised to possess the same essential pharmacophoric features of colchicine binding site inhibitors.

Development of Biphenylthiazoles Exhibiting Improved Pharmacokinetics and Potent Activity Against Intracellular .

Exploring the structure-activity relationship (SAR) at the cationic part of arylthiazole antibiotics revealed hydrazine as an active moiety. The main objective of the study is to overcome the inherited toxicity associated with the free hydrazine. A series of hydrocarbon bridges was inserted in between the groups, to separate the two amino groups.

Oxadiazolylthiazoles as novel and selective antifungal agents.

Studying the structure-activity relationships (SAR) of oxadiazolylthiazole antibiotics unexpectedly led us to identify ethylenediamine- and propylenediamine-analogs as potential antimycotic novel lead structures. Replacement of the ethylenediamine moiety for the lead compound 7 with cis-diaminocyclohexyl group (compound 18) significantly enhanced the antifungal activity. In addition to the high safety margin of 18 against mammalian cells, it showed highly selective broad-spectrum activity against fungal cells without inhibiting the human normal microbiota.

Synthesis and antibacterial evaluation of a novel library of 2-(thiazol-5-yl)-1,3,4-oxadiazole derivatives against methicillin-resistant Staphylococcus aureus (MRSA).

Replacement of the n-butylphenyl moiety in the lipophilic part of the previously reported arylthiazole antibiotics with naphthyl ring amended its activity against vancomycin resistant strains of Staphylococcus aureus. Incorporation of the CN linker connecting the nitrogenous head with thiazole within an oxadiazole ring provided orally available analogs with relatively long half-life. In this article, a set of new twenty-three derivatives of 2-(thiazol-5-yl)-1,3,4-oxadiazole was synthesized combining both structural modifications in one new scaffold with the objectives of enhancing both the pharmacokinetic profile and antibacterial activities vs.

Phenylthiazoles with nitrogenous side chain: An approach to overcome molecular obesity.

A novel series of phenylthiazoles bearing cyclic amines at the phenyl-4 position was prepared with the objective of decreasing lipophilicity and improving the overall physicochemical properties and pharmacokinetic profile of the compounds. Briefly, the piperidine ring (compounds 10 and 12) provided the best ring size in terms of antibacterial activity when tested against 16 multidrug-resistant clinical isolates. Both compounds were superior to vancomycin in the ability to eliminate methicillin-resistant Staphylococcus aureus (MRSA), residing within infected macrophages and to disrupt mature MRSA biofilm.