Discovery and Anticancer Screening of Novel Oxindole-Based Derivative Bearing Pyridyl Group as Potent and Selective Dual FLT3/CDK2 Kinase Inhibitor.

Protein kinases regulate cellular activities and make up over 60% of oncoproteins and proto-oncoproteins. Among these kinases, FLT3 is a member of class III receptor tyrosine kinase family which is abundantly expressed in individuals with acute leukemia. Our previous oxindole-based hit has a particular affinity toward FLT3 (IC = 2.

A Deeper Insight into , , and Variants and Genotype-Phenotype Correlation of a Turkish Cohort with Alport Syndrome.

Introduction: Alport syndrome (AS) is an inherited, rare, progressive kidney disease that affects the eye and ear physiology. Pathogenic variants of account for 85% of all cases, while and account for the remaining 15%.

Methods: Targeted next-generation sequencing of the , , and genes was performed in 125 Turkish patients with AS.

Combination of an Oxindole Derivative with (-)-β-Elemene Alters Cell Death Pathways in FLT3/ITD Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is one of the cancers that grow most aggressively. The challenges in AML management are huge, despite many treatment options. Mutations in FLT3 tyrosine kinase receptors make the currently available therapies less responsive.

The evidence for repurposing anti-epileptic drugs to target cancer.

Antiepileptic drugs are versatile drugs with the potential to be used in functional drug formulations with drug repurposing approaches. In the present review, we investigated the anticancer properties of antiepileptic drugs and interlinked cancer and epileptic pathways. Our focus was primarily on those drugs that have entered clinical trials with positive results and those that provided good results in preclinical studies.

Vanillin-Based Indolin-2-one Derivative Bearing a Pyridyl Moiety as a Promising Anti-Breast Cancer Agent via Anti-Estrogenic Activity.

The structure-based design introduced indoles as an essential motif in designing new selective estrogen receptor modulators employed for treating breast cancer. Therefore, here, a series of synthesized vanillin-substituted indolin-2-ones were screened against the NCI-60 cancer cell panel followed by in vivo, in vitro, and in silico studies. Physicochemical parameters were evaluated with HPLC and SwissADME tools.

Discovery of oxindole-based FLT3 inhibitors as a promising therapeutic lead for acute myeloid leukemia carrying the oncogenic ITD mutation.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately 30% of acute myeloid leukemia (AML) patients. In the current study, the oxindole chemotype is employed as a structural motif for the design of new FLT3 inhibitors as potential hits for AML irradiation. Cell-based screening was performed with 18 oxindole derivatives and 5a-c inhibited 68%-73% and 83%-91% of internal tandem duplication (ITD)-mutated MV4-11 cell growth for 48- and 72-h treatments while only 0%-2% and 27%-39% in wild-type THP-1 cells.

The SARS-CoV-2 mutations versus vaccine effectiveness: New opportunities to new challenges.

Background: The SARS-CoV-2 coronavirus epidemic is hastening the discovery of the most efficient vaccines. The development of cost-effective vaccines seems to be the only solution to terminate this pandemic. However, the vaccines' effectiveness has been questioned due to recurrent mutations in the SARS-CoV-2 genome.

Drugs repurposed: An advanced step towards the treatment of breast cancer and associated challenges.

Breast cancer (BC) is mostly observed in women and is responsible for huge mortality in women subjects globally. Due to the continued development of drug resistance and other contributing factors, the scientific community needs to look for new alternatives, and drug repurposing is one of the best opportunities. Here we light upon the drug repurposing with a major focus on breast cancer.

Role of autophagy and evaluation the effects of microRNAs 214, 132, 34c and prorenin receptor in a rat model of focal segmental glomerulosclerosis.

Aims: Focal segmental glomerulosclerosis (FSGS) is the common cause of chronic renal disease worldwide. Although there are many etiologic factors which have common theme of podocyte injury conclusive etiology is not clearly understood. In this study, we aimed to explore the role of autophagy in the pathogenesis of podocyte injury, which is the key point in disease progression, and the roles of intrarenal microRNAs and the prorenin receptor (PRR) in the 5/6 nephrectomy and adriamycin nephropathy models of FSGS.

Chemical, biological and molecular modelling analyses to probe into the pharmacological potential of Antidesma madagascariense Lam.: A multifunctional agent for developing novel therapeutic formulations.

Antidesma madagascariense Lam. (AM), an indigenous medicinal plant to the Mascarene Islands, is used for the treatment of several diseases. We endeavoured to validate its use via evaluating the kinetics of inhibition of crude aqueous extract (CAE) and crude methanol extract (CME) of AM against key metabolic enzymes (pancreatic lipase, cholesterol esterase [CEase], acetylcholinesterase [AChE], and urease).

Integration of in vitro and in silico perspectives to explain chemical characterization, biological potential and anticancer effects of Hypericum salsugineum: A pharmacologically active source for functional drug formulations.

The genus Hypericum is one of the most popular genera in both traditional medicine and scientific platform. This study is designed to provide conceptual insights on the biological potential and chemical characterization of H. salsugineum, which is endemic to Turkey.

UHPLC-QTOF-MS analysis of bioactive constituents from two Romanian Goji (Lycium barbarum L.) berries cultivars and their antioxidant, enzyme inhibitory, and real-time cytotoxicological evaluation.

Goji (Lycium barbarum L.) berries are emphasized as healthy food or are used widely as dietary supplements. In the present study, the antioxidant and enzyme inhibitory activities of berries extracts from two selected Romanian cultivars (cv.

Functional analysis of ESM1 by siRNA knockdown in primary and metastatic head and neck cancer cells.

Background: Genetic factors play a large role in cancer, and thus, there is a great desire to understand the effects of different genes in cancer and to also develop gene therapy for better treatments. Therefore, the development of alternative diagnosis and therapy modalities is of utmost importance. The aim of our study was to illuminate the role of ESM1 (endothelial cell-specific molecule-1, also known as Endocan) in proliferation and migration of head and neck cancer, thus helping to pave the way for new treatment modalities and predictive biomarkers.

Traditionally Used Species: Phytochemical Composition, Antioxidant Activity, Enzyme Inhibitory Properties, Cytotoxic Effects, and Studies of and .

Members of the genus are used as food and as traditional medicines. In order to find new sources of biologically-active compounds, chemical and biological profiles of two species ( and were investigated. Chemical profiles were evaluated by HPLC-ESI-MS, as well as by their total phenolic and flavonoid contents.

Multiple pharmacological targets, cytotoxicity, and phytochemical profile of Aphloia theiformis (Vahl.) Benn.

Aphloia theiformis (Vahl.) Benn. (AT) is traditionally used in Sub-Saharan African countries including Mauritius as a biomedicine for the management of several diseases.