Current Medicinal Chemistry - Online First

Indole is considered the most promising scaffold for anticancer drug design due to its high bioavailability, unique chemical properties, and broad spectrum of pharmacological action.

Twelve novel thiazole-containing the 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives as sunitinib analogs were designed and synthesized, and their anticancer activity was evaluated against the NCI-60 cancer cell lines.

The thiazole-contained 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives were synthesized using Knoevenagel condensation of 1,3-thiazole-5-carboxylic acid 1. Their anticancer activities were evaluated by NCI-60 one-dose screen assay. The molecular docking studies were performed using AutoDock tools and the AutoDock Vina programs. The ADMETlab 2.0 web server predicted the physicochemical properties of compounds.

Among the synthesized new 5-fluoro-2-oxindole derivatives, compound 3g demonstrated high antitumor activity (GI>70%) against eight types of cancer: leukemia, breast cancer, ovarian cancer, lung cancer, melanoma, CNS cancer, renal cancer, and colon cancer. The most activity was observed against breast cancer (T-47D, GI=96.17%), lung cancer (HOP-92, GI=95.95%), ovarian cancer (NCI/ADR-RES, GI=95.13%), and CNS cancer (SNB-75, GI=89.91%). The molecular docking results of compound 3g demonstrated the possibility of inhibiting VEGF2 receptors as his potential anticancer mechanism. The physicochemical properties predicted for compounds 3f and 3g showed positive results.

Compound 3g demonstrated high in vitro NCI-60 anticancer activity against nine cancer types and showed cell growth inhibition against leukemia, CNS, and breast cancer at 6 - 31% higher than Sunitinib, and may represent the basis for further modification of the thiazole-containing analogs of the anticancer drug Sunitinib.

Astragalus membranaceus has shown positive clinical efficacy in treating colorectal cancer (CRC).

This study aimed to identify the key active components of Astragalus and determine effective targets of these components in CRC patients.

We identified active components of Astragalus membranaceus and differentially expressed genes in traditional Chinese medicine systems pharmacology database and The Cancer Genome Atlas. Additionally, the enrichment analysis of differential target genes (DTGs) was performed using the R-package clusterProfiler. Immunocyte correlation analysis and non-coding regulatory network construction were performed for biomarkers using Spearman’s method and NetworkAnalyst. Finally, molecular docking of biomarkers and their corresponding molecule drugs was done with Autodock Vina software.

We identified 20 active components of Astragalus membranaceus and 1 403 target genes through screening. A total of 2 300 differentially expressed genes, and 3 035 hub genes in CRC were screened. The integration of the target genes with the significantly differentially expressed genes and Hub genes identified resulted in a total of 86 DTGs. Subsequently, the results showed 828 enriched GO biological processes, 184 enriched GO molecular functions, 59 enriched GO cellular components, and 46 enriched KEGG pathways. We also obtained a total of 143 PPI pairs involving 67 nodes. Additionally, we constructed 45 mRNA-TF pairs, 101 miRNA-mRNA pairs, and 200 miRNA-mRNA-TF triplets. Finally, molecular docking was performed for the active component quercetin with F2 and UGT1A1 and formic acid with FGA, AHSG, and KNG1.

This study identified the active components of Astragalus membranaceus and their corresponding targets in CRC. These findings provide robust evidence for precision drug therapy in patients with CRC.

microRNAs (miRNAs) are a class of non-coding RNAs that play important roles in gene regulation. miRNAs are transcribed from DNA sequences into primary miRNAs and then processed into precursor miRNAs and mature miRNAs. miRNA gene counts in chromosomes for different species have been studied.

Certain chromosomes have higher numbers of miRNA genes in all species, such as the X chromosome, while the Y chromosome has the fewest or no miRNA genes. miRNA counts in different chromosomes might have a positive correlation with coding gene counts in many species. In this study, a regression model was used to find the relationship between the miRNA count and the coding gene count across human chromosomes, and miRNA counts for 23 human chromosomes were predicted based on this regression model. In addition, the chromosome locations for the miRNA biomarkers of major depression, diabetes, Parkinson’s disease, and COVID-19 are discussed.

The results reveal that miRNA biomarkers of these diseases are located in various chromosomes. The dispersion of miRNA locations across different chromosomes might explain the complication of the pathology of these diseases. Moreover, diabetes and COVID-19 have the largest number of miRNA biomarkers from Chromosome X.

As Chromosome X is a sex chromosome, this phenomenon may explain the gender difference in the prevalence or severity of diabetes and COVID-19. The significant gender difference in the prevalence or severity of diabetes and COVID-19 might be due to the regulation function of their miRNA biomarkers from Chromosome X.

Prosopis juliflora has been employed in many traditional treatments. As evidenced by our earlier research, Prosopis juliflora leaf methanol extract (PJME) has a promising future in the fight against lung cancer. It may also be used in conjunction with other treatments to effectively manage lung cancer. Aims and objective: The main objective of this study was to explore the potential of PJME to inhibit lung cancer in A549 cells, along with its underlying mechanisms of action.

The antiproliferative effects were determined using MTT and LDH tests. Apoptosis-inducing capacity was evaluated using the DAPI staining, caspase-3 test, cytochrome C assay, PARP cleavage, and qRT-PCR. To investigate the mechanism of action of PJME in lung cancer, the levels of ROS, MMP, GSH, MDA, and specific ferroptosis indicators were measured.

The experimental data of the current study indicated that exposure of A549 cells to PJME reduced cell viability and increased cellular cytotoxicity. The apoptosis-inducing ability of PJME in A549 cells was validated by enhanced nuclear condensation, level of the caspase-3, cytochrome C, and PARP release. In addition, qRT-PCR investigations verified that the administration of PJME led to a decrease in the expression of anti-apoptotic gene Bcl2 while enhancing the mRNA level of pro-apoptotic genes, such as Bax and caspase-3, in A549 cells.

The study also found that PJME has the ability to activate ferroptosis pathways, as evidenced by elevated reactive oxygen species (ROS) generation, changes in the levels of antioxidant markers (MDA and GSH), and decreased expression of SLC7A11 and GPX4. The results of the present study clearly showed that PJME inhibited the proliferation of A549 cells and induced ferroptosis by reducing the expression of the important targets SLC7A11 and GPX4. Further research is necessary to fully understand the clinical efficacy of PJME before it can be investigated as supplemental or adjuvant therapy for lung cancer.

Alzheimer's disease (AD) is the most common neurodegenerative disease in older people, characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of aggregated of hyperphosphorylated tau protein, which normally helps stabilize microtubules in neurons.

Nowadays, artemisinin (ART) as well as its semisynthetic derivatives (ARTs) are seen as potential neuroprotectors. The goal of the present study is the assessment of neuroprotective, antibacterial activity of ART, as well as in silico studies of ART affinity to Aβ-peptides and the search of potential targets for ART. The study is referring to explores the impact of ART on an animal model of AD that is induced by the aggregated amyloidogenic peptide Aβ1-42 by electrophysiology and morphology analysis. Specifically, the focus is on the activation of the entorhinal cortex (ENT) as synaptic potentiation.

Electrophysiological and histochemical have demonstrated that therapeutic injection of ART or its derivatives acts as a neuroprotective This treatment appears to prevent or slow down damage to brain tissue, and it promotes the restoration of neurons and their surrounding environment. The protective effects of ART may involve various mechanisms, including antioxidant activity, anti-inflammatory effects, and the inhibition of apoptosis.

in silico studies revealed a direct, strong interaction of ART with the amyloidogenic peptides 5Aβ17-42, 12Aβ9-40, and 18Aβ9-40. in silico screening revealed several protein targets for ART, including cytochrome P-450 2B6 (CYP2B6). The highest binding affinity was found on the active site of CYP2B6. ART has great potential for discovering new drugs using combined therapies.

Tyrosine kinase inhibitors (TKIs) target certain cell signalling pathways, and have become a promising class of medications for the treatment of cancer in recent years. Because of their distinct structure and adaptable chemistry, pyrazolines have drawn a lot of interest from organic and medicinal chemists. Their exceptional TKI activity has prompted them to investigate chemotherapy for cancer.

We aim to develop agents that inhibit tyrosine kinases highly effective with the least amount of harm possible, perhaps improving the course of cancer treatment.

This review compiled current information from recent literature sources, including in vitro, in vivo, approved medications, active clinical trials, and the structure-activity relationships (SAR) linked to various pyrazoline analogues used as small-molecule Tyrosine Kinase Inhibitors in cancer treatment.

This study focuses on SAR inside the pyrazoline ring and its derivatives as TKIs, and it emphasizes current developments, including patents, authorized medications, and compounds in clinical trials.

By enhancing our understanding of these compounds, our goal is to aid in making the roles of pharmacologists, scientists, and researchers who are designing and developing next-generation anticancer drugs with pyrazoline scaffolds easier. The future holds immense potential for the continued evolution of pyrazoline-based therapies, offering renewed hope in the ongoing battle against cancer.