Design, synthesis, molecular docking, and molecular dynamic studies of novel quinazoline derivatives as phosphodiesterase 7 inhibitors.

Phosphodiesterase 7 (PDE7) is a high-affinity cyclic AMP (cAMP)-specific PDE that is expressed in immune and proinflammatory cells. In this work, we explore the possibility that selective small molecule inhibitors of this enzyme family could provide a novel approach to alleviate the inflammation that is associated with many inflammatory diseases. A series of novel substituted 4-hydrazinoquinazoline derivatives and fused triazoloquinazolines were designed, synthesized, and evaluated for their PDE7A inhibition activities, in comparison with Theophylline, a non-selective PDE inhibitor, and BRL50481, a selective PDE7A inhibitor.

Design, synthesis and in vitro anticancer activity of some new lomefloxacin derivatives.

Our main goal was to design and synthesize novel lomefloxacin derivatives that inhibit the topoisomerase II enzyme, leading to potent anticancer activity. Lomefloxacin derivatives substituted at position 3 and 7 were synthesized and screened for cytotoxic activity utilizing 60 different human cancer cell lines. Furthermore, compounds 3a,b,c,e that revealed potent broad-spectrum anticancer activity (with mean percent GI more than 47%) were further evaluated using five dose concentrations and calculating the GI.

Assessment of commitment to healthy daily habits and diets, preventive measures, and beliefs about natural products utilization during COVID-19 pandemic in certain population in Egypt and Saudi Arabia.

Objective: The purpose of this research is to assess the commitment of participants in Saudi Arabia and Egypt towards healthy daily habits, preventive measures, healthy food habits, and beliefs about natural products as an immunostimulants during COVID-19 pandemic.

Method: A cross-sectional questionnaire-based study was conducted in Saudi Arabia (mainly Riyadh and Jeddah) and Egypt (mainly Cairo). The questionnaire instrument was created based on an extensive literature review on the COVID-19 pandemic, including its spreading and transmission methods, preventive measures, healthy lifestyle, and diets that increase human immunity against viral infections and the use of natural products and drinks.

Schiff bases as linker in the development of quinoline-sulfonamide hybrids as selective cancer-associated carbonic anhydrase isoforms IX/XII inhibitors: A new regioisomerism tactic.

A novel set of quinoline tailored with the sulfonamide as zinc-binding group (ZBG) has been rationalized and synthesized as carbonic anhydrase (CA, EC 4.2.1.

Selective COX-2 Inhibitors: Road from Success to Controversy and the Quest for Repurposing.

The introduction of selective COX-2 inhibitors (so-called 'coxibs') has demonstrated tremendous commercial success due to their claimed lower potential of serious gastrointestinal adverse effects than traditional NSAIDs. However, following the repeated questioning on safety concerns, the coxibs 'controversial me-too' saga increased substantially, inferring to the risk of cardiovascular complications, subsequently leading to the voluntary withdrawal of coxibs (e.g.

In Vitro Anticancer Activity Screening of Novel Fused Thiophene Derivatives as VEGFR-2/AKT Dual Inhibitors and Apoptosis Inducers.

Protein kinases are seen as promising targets in controlling cell proliferation and survival in treating cancer where fused thiophene synthon was utilized in many kinase inhibitors approved by the FDA. Accordingly, this work focused on adopting fused thienopyrrole and pyrrolothienopyrimidine scaffolds in preparing new inhibitors, which were evaluated as antiproliferative agents in the HepG2 and PC-3 cell lines. The compounds (IC = 3.

Anti-inflammatory activity of pyridazinones: A review.

The pyridazinone core has emerged as a leading structure for fighting inflammation, with low ulcerogenic effects. Moreover, easy functionalization of various ring positions of the pyridazinone core structure makes it an attractive synthetic and therapeutic target for the design and synthesis of anti-inflammatory agents. The present review surveys the recent advances of pyridazinone derivatives as potential anti-inflammatory agents to provide insights into the rational design of more effective anti-inflammatory pyridazinones.

Design, Synthesis, and Antipoliferative Activities of Novel Substituted Imidazole-Thione Linked Benzotriazole Derivatives.

A new series of benzotriazole moiety bearing substituted imidazol-2-thiones at N1 has been designed, synthesized and evaluated for in vitro anticancer activity against the different cancer cell lines MCF-7(breast cancer), HL-60 (Human promyelocytic leukemia), and HCT-116 (colon cancer). Most of the benzotriazole analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, showed potent activity against the cancer cell lines such as MCF-7, HL-60 and HCT-116 with IC 3.

New promising levofloxacin derivatives: Design, synthesis, cytotoxic activity screening, Topo2β polymerase inhibition assay, cell cycle apoptosis profile analysis.

Newly designed levofloxacin analogues were synthesized to act as topoisomerase II beta inhibitors (Topo2β). Their cytotoxic activity was screened against breast, liver, and leukemia cancer cell lines. The best activity against liver cancer cell line (Hep3B) was exhibited by the target compounds 3c, 3e, 4a, and 6d (IC = 2.

New pyridazine derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents; design, synthesis and biological evaluation.

New pyridazinone and pyridazinthione derivatives were designed, synthesized and identified through performing H NMR, C NMR, IR and MS spectroscopic techniques. All the newly synthesized derivatives were evaluated for cyclooxygenase inhibitory activity and COX-2 selectivity using celecoxib and indomethacin, as reference drugs. All compounds showed highly potent COX-2 inhibitory activity with IC values in nano-molar range.

Synthesis and biological evaluation of pyridazinone derivatives as selective COX-2 inhibitors and potential anti-inflammatory agents.

A series of pyridazinone derivatives, bearing an aryl or pyridyl moiety linked through an ethenyl spacer to position-6 was designed and synthesized. The newly synthesized compounds were screened for preferential inhibition of COX-2 over COX-1 isoforms. Compounds 2c, 2d, 2e, 2f, 3a, 3b, 3c, 3d and 3e are highly potent COX-2 inhibitors with IC values in nano-molar range.

Novel nalidixic acid derivatives targeting topoisomerase II enzyme; Design, synthesis, anticancer activity and effect on cell cycle profile.

Aim: Design and synthesis of novel nalidixic acid derivatives of potent anticancer and topoisomerase II inhibitory activities were our major aim.

Materials & Methods: All the newly synthesized nalidixic acid derivatives were submitted to the National Cancer Institute (NCI), Bethesda, USA and were accepted for single dose screening. Further investigation via IC determination of the most potent compound 6a against K-562 and SR leukemia cell lines.

Synthesis of Novel Thieno[2,3-d]pyrimidine Derivatives and Evaluation of Their Cytotoxicity and EGFR Inhibitory Activity.

Background: 4-Substitutedaminoquinazoline scaffolds were reported to possess potent cytotoxic and EGFR inhibitory activity such as gefitinib (Iressa), erlotinib (Tarceva) and tandutinib.

Objective: Synthesis of novel 4-substitutedaminothieno[2,3-d]pyrimidine derivatives as bioisosters of 4-substitutedaminoquinazoline derivatives with potential cytotoxic and EGFR inhibitory activity.

Methods: Novel 4-substitutedaminothieno[2,3-d]pyrimidine derivatives 4a-i and 5a-c were synthesized via reacting corresponding 4-chlorothieno[2,3-d]pyrimidine derivatives 3a-c with N-methylpiperazine, morpholine, N-phenylpiperazine or 1,3-propanediamine.

Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers.

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal cancer cell line (Caco-2). All the synthesized compounds showed better activity than the reference standards (Doxorubicin and 5-FU).

Synthesis, Anticancer Activity, Effect on Cell Cycle Profile, and Apoptosis-Inducing Ability of Novel Hexahydrocyclooctathieno[2,3-d]pyrimidine Derivatives.

A novel series of hexahydrocyclooctathieno[2,3-d]pyrimidines was synthesized. Investigation of the anticancer activity of these derivatives revealed that compounds 2a and b showed broad-spectrum anticancer activity in nanomolar to micromolar concentrations. In particular, compound 2b showed a concentration required for 50% inhibition of cell growth (GI50) value of less than 1 µM against 20 cancer cell lines.

Design, Synthesis and Biological Evaluation of New Thieno[2,3- d]pyrimidines as Anti-inflammatory Agents.

Background: Long term use of NSAIDS is mainly accompanied by major health implications such as gastrointestinal erosions, ulcerations and nephrotoxicity. These side effects arise from local irritation by the carboxylic acid moiety, that is common to most of NSAIDs (topical effect), in addition to decreased cytoprotective prostaglandin production. Therefore, in the medicinal chemistry research area, there is an ongoing need for the discovery of new, potent and safer anti-inflammatory lead compounds devoid of the irritant carboxylic acid moiety.

Novel tacrine analogs as potential cholinesterase inhibitors in Alzheimer's disease.

Acetylcholinesterase inhibitors (AChEIs) are used for the treatment of Alzheimer's disease (AD). The increase in ACh levels ameliorates the symptoms of the disease. Tacrine is the first clinically approved drug as AChEI used in the treatment of AD.

Design, synthesis, and molecular-modeling study of aminothienopyridine analogues of tacrine for Alzheimer's disease.

2-Amino-3-cyanothiophenes were successfully condensed with a number of cycloalkanones to afford tacrine analogues in a one-step reaction mediated with Lewis acid. The newly synthesized compounds have been tested for their ability to inhibit acetylcholine esterase (AChE) activity using tacrine as standard drug. Some of the tested compounds showed moderate inhibitory activity in comparison with tacrine, especially compounds 6a which displayed the highest inhibitory activity.