Synthesis of Silver Nano Particles Using Myricetin and the In-Vitro Assessment of Anti-Colorectal Cancer Activity: In-Silico Integration.

The creation of novel anticancer treatments for a variety of human illnesses, including different malignancies and dangerous microbes, also potentially depends on nanoparticles including silver. Recently, it has been successful to biologically synthesize metal nanoparticles using plant extracts. The natural flavonoid 3,3', 4', 5,5', and 7 hexahydroxyflavon (myricetin) has anticancer properties. There is not much known about the regulatory effects of myricetin on the possible cell fate-determination mechanisms (such as apoptosis/proliferation) in colorectal cancer. Because the majority of investigations related to the anticancer activity of myricetin have dominantly focused on the enhancement of tumor cell uncontrolled growth (i.e., apoptosis). Thus, we have decided to explore the potential myricetin interactors and the associated biological functions by using an in-silico approach. Then, we focused on the main goal of the work which involved the synthesis of silver nanoparticles and the labeling of myricetin with it. The synthesized silver nanoparticles were examined using UV-visible spectroscopy, dynamic light scattering spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. In this study, we have investigated the effects of myricetin on colorectal cancer where numerous techniques were used to show myricetin's effect on colon cancer cells. Transmission Electron Microscopy was employed to monitor morphological changes. Furthermore, we have combined the results of the colorectal cancer gene expression dataset with those of the myricetin interactors and pathways. Based on the results, we conclude that myricetin is able to efficiently kill human colorectal cancer cell lines. Since, it shares important biological roles and possible route components and this myricetin may be a promising herbal treatment for colorectal cancer as per an in-silico analysis of the TCGA dataset.

A Network-Guided Approach to Discover Phytochemical-Based Anticancer Therapy: Targeting MARK4 for Hepatocellular Carcinoma.

MAP/microtubule affinity-regulating kinase 4 (MARK4) is associated with various biological functions, including neuronal migration, cell polarity, microtubule dynamics, apoptosis, and cell cycle regulation, specifically in the G1/S checkpoint, cell signaling, and differentiation. It plays a critical role in different types of cancers. Hepatocellular carcinoma (HCC) is the one of the most common forms of liver cancer caused due to mutations, epigenetic aberrations, and altered gene expression patterns. Here, we have applied an integrated network biology approach to see the potential links of MARK4 in HCC, and subsequently identified potential herbal drugs. This work focuses on the naturally-derived compounds from medicinal plants and their properties, making them targets for potential anti-hepatocellular treatments. We further analyzed the HCC mutated genes from the TCGA database by using cBioPortal and mapped out the MARK4 targets among the mutated list. MARK4 and Mimosin, Quercetin, and Resveratrol could potentially interact with critical cancer-associated proteins. A set of the hepatocellular carcinoma altered genes is directly the part of infection, inflammation, immune systems, and cancer pathways. Finally, we conclude that among all these drugs, Gingerol and Fisetin appear to be the highly promising drugs against MARK4-based targets, followed by Quercetin, Resveratrol, and Apigenin.

Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies.

In present study a series of triazolopyrimidine-quinoline and cyanopyridine-quinoline hybrids were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d), strongly inhibited AChE with IC50 value of 42 nM. Furthermore compound 10d was identified as most promising compound with 12 fold selectivity against butyrylcholinesterase (BuChE). This compound displayed a composed multitargeted profile with promising inhibition of self-induced and AChE - induced Aß aggregation and antioxidant activity.