New 4-amino-3-chloro benzoate ester derivatives as EGFR inhibitors: synthesis, in silico and biological analyses.

Aim: The main goal of this study was to synthesize new derivatives of 4-amino-3-chloro benzoate ester, including 1,3,4-oxadiazole derivatives (), benzohydrazone derivatives (), and hydrazine-1-carbothioamide derivatives () that target epidermal growth factor receptor (EGFR) tyrosine kinase.

Materials & Methods: The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR, and the anti-proliferative properties were tested in vitro.

Anti-proliferation evaluation of new derivatives of indole-6-carboxylate ester as receptor tyrosine kinase inhibitors.

The main goal was to create two new groups of indole derivatives, hydrazine-1-carbothioamide ( and ) and oxadiazole (, and ) that target EGFR (, , ) or VEGFR-2 (). The new derivatives were characterized using various spectroscopic techniques. Docking studies were used to investigate the binding patterns to EGFR/VEGFR-2, and the anti-proliferative properties were tested .

Novel 1,3,4-oxadiazole derivatives of naproxen targeting EGFR: Synthesis, molecular docking studies, and cytotoxic evaluation.

The close association between inflammation and cancer inspired the synthesis of a series of 1,3,4-oxadiazole derivatives (compounds H4-A-F) of 6-methoxynaphtalene. The chemical structures of the new compounds were validated utilizing Fourier-transform infrared, proton nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance spectroscopic techniques and CHN analysis. Computer-aided drug design methods were used to predict the compounds biological target, ADMET properties, toxicity, and to evaluate the molecular similarities between the design compounds and erlotinib, a standard epidermal growth factor receptor (EGFR) inhibitor.

New Carbothioamide and Carboxamide Derivatives of 3-Phenoxybenzoic Acid as Potent VEGFR-2 Inhibitors: Synthesis, Molecular Docking, and Cytotoxicity Assessment.

Introduction/background: Because of the well-established link between angiogenesis and tumor development, the use of antiangiogenic therapeutics, such as those targeting VEGFR-2, presents a promising approach to cancer treatment. In the current study, a set of five hydrazine-1-- carbothioamide (compounds 3a-e) and three hydrazine-1-carboxamide derivatives (compounds 4a-c) were successfully synthesized from 3-phenoxybenzoic acid. These compounds were specially created as antiproliferative agents with the goal of targeting cancer cells by inhibiting VEGFR-2 tyrosine kinase.

Synthesis, Prediction, and Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors.

Introduction: Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies.

Methods: A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, HNMR, CNMR, and HR-mass spectroscopy.

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors.

Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (4a-d) and benzamides derivatives (5a-e) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, H nuclear magnetic resonance (NMR), C NMR, and mass spectra; and various physicochemical properties were determined.

New Indole-6-Carboxylic Acid Derivatives as Multi-Target Antiproliferative Agents: Synthesis, in Silico Studies, and Cytotoxicity Evaluation.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, H-NMR, CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors.

Antitumor activity of the new tyrphostin briva against BRAF-mutant colorectal carcinoma cells.

Because of a reduced sensitivity of BRAF-mutant colorectal cancers to BRAF inhibitor treatment when compared with BRAF-mutant melanoma, it is essential to develop efficient drugs to cope with this disease. The new 2-(4-bromophenyl)-3-arylacrylonitrile compound Briva was prepared in one step from commercially available starting compounds. Briva and two known thiophene analogs (Thio-Iva and Thio-Dam) were tested for their cytotoxic activity against various tumor cell lines including colorectal and breast cancer cells.

-repeat polymorphism in the tissue plasminogen activator () gene, seminal t-PA concentration, and male fertility impairment: A case-control study.

Background: Tissue plasminogen activator (t-PA) is a protein involved in the fibrinolytic system that catalyzes the conversion of plasminogen into the active plasmin. The activity of t-PA is controlled by plasminogen activator inhibitor-1. t-PA has crucial functions during spermatogenesis.

Biological activity and apoptotic signaling pathway of C-functionalized cephalostatin 1 analogues.

Cephalostatin 1, a potent anti-cancer agent, is a natural bis-steroidal alkaloid that causes cell death in the subnanomolar to picomolar ranges via an atypical apoptosis pathway. Although cephalostatin 1 is a highly effective anticancer drug, its availability limits its utilization. We previously reported the synthesis of two 12'α-hydroxy derivatives of cephalostatin 1 that induce cell death by activating the ER stress apoptosis signaling pathway.

Alu DNA Polymorphism of Human Tissue Plasminogen Activator (tPA) Gene in Diabetic Jordanian Patients.

Background: Hypercoagulability and hypofibrinolysis are among the symptoms exhibited by diabetic patients. Our study aimed to address the polymorphic nature of Alu DNA fragment in the human tissue plasminogen activator gene within diabetes mellitus (DM) Jordanian patients.

Methods: Genomic DNA was isolated from 76 DM patients and 60 non-diabetic Jordanian individuals, and the Alu fragment was amplified using PCR.

Cephalostatin 1 analogues activate apoptosis via the endoplasmic reticulum stress signaling pathway.

The current study was conducted to compare the cytotoxicity of two stereospecific cephalostatin 1 analogues (CAs) against several human normal cell types and cancer cell lines and to determine their cytotoxic mechanism. Both CA analogues induced apoptosis and were cytotoxic with 50% growth inhibition (GI) at ~1µM or less in six human cancer cell lines but neither analogue at 10µM killed more than 14% of any of three types of normal human cells suggesting their cytotoxicity is cancer-specific. CA treatment inhibited clonogenic tumor growth and activated caspase 3 and 9 but not caspase 8.

Anti-spermatogenic activities of Taraxacum officinale whole plant and leaves aqueous extracts.

Taraxacum officinale has been used in Jordan folk medicine to treat male infertility. A recent study has proved a contradictory effect of the whole plant aqueous extract. The aim of the current study was to determine if the leaves of T.

2-deoxy-D-Glucose Synergizes with Doxorubicin or L-Buthionine Sulfoximine to Reduce Adhesion and Migration of Breast Cancer Cells.

Background: Cancer metastasis depends on cell motility which is driven by cycles of actin polymerization and depolymerization. Reactive oxygen species (ROS) and metabolic oxidative stress have long been associated with cancer. ROS play a vital role in regulating actin dynamics that are sensitive to oxidative modification.

Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells.

Background: ADF/cofilin proteins are key modulators of actin dynamics in metastasis and invasion of cancer cells. Here we focused on the roles of ADF and cofilin-1 individually in the development of polarized migration of rat mammary adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein. Small interference RNA (siRNA) technology was used to knockdown (KD) the expression of ADF and cofilin-1 independently.

Rates of infection and phylogenetic analysis of GB virus-C among Kuwaiti and Jordanian blood donors.

Objectives: GB virus-C/hepatitis G virus (GBV-C/HGV), collectively known as GBV-C, has been reported to be associated with non-A-E hepatitis. The aim of this study was to determine the rate of infection and genotypic characteristics of GBV-C among Kuwaiti and Jordanian blood donors.

Methods: A total of 334 plasma/serum samples from healthy blood donors in Kuwait (n = 130) and Jordan (n = 204) were screened using RT-PCR/nested PCR of the 5'-untranslated region (5'-UTR).

Prevalence and risk factors for anabolic-androgenic steroid abuse among Jordanian collegiate students and athletes.

Background: The study was conducted to measure the extent of androgenic steroids abuse among two targeted groups in Jordan, college students and athletes, and the risk factors associated with this abuse.

Methods: Five hundred and three Jordanian collegiate students and 154 bodybuilding athletes completed a three section questionnaire that investigated demographic information, prevalence of anabolic-androgenic steroids (AAS) and attitude towards steroids abuse.

Results: Of the investigated collegiate students, 4.

Allele frequency distribution and haplotype of eleven hemizygous short tandem repeats in Jordanians.

The haplotype and allele frequency distributions of the Y-chromosomal STR markers DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, and DYS439 were determined in a sample of 97 unrelated males from Jordan.

A rapid PCR-based method for identification of four important Candida species.

The rapid detection and identification of Candida species in clinical laboratories are extremely important for the management of patients with hematogenous candidosis. Currently available culture and biochemical methods for detection and identification of Candida species are time-consuming. This study describes the use of a simple and rapid PCR method using species-specific oligonucleotides for the detection of clinical isolates of Candida species.

African Jordanian population genetic database on fifteen short tandem repeat genetic loci.

Aim: To establish a genetic database of the African-Jordanian population for forensic and paternity testing purposes.

Method: Allelic distribution at fifteen short tandem repeat (STR) loci was determined for 95 healthy unrelated African-Jordanians. The 15 autosomal STR loci, included within the GenePrint PowerPlex 16 system, were amplified from the subset of the 95 DNA extracts isolated from the population sample.

Jordanian population data on five STR forensic loci: D16S539, TPOX, CSF1PO, Penta D, and Penta E.

The allele distributions at five STR loci, D16S539, TPOX, CSF1PO, Penta D, and Penta E have been determined. None of the five loci were found to deviate from Hardy-Weinberg expectations according to the results of the G (homogeneity) test.