Current Chemical Biology - Volume 15, Issue 2, 2021

Innumerable reasons have been reported that affect and infect the liver and cause liver diseases. The evaluation and follow-up of liver fibrosis and cirrhosis have been traditionally performed by liver biopsy. However, it has become evident that this once defined as “gold-standard” is now not the best method as it involves many limitations. Attempts to reveal non-invasive diagnostic tools have generated serum biomarkers, multiple scores, formulae, and imaging modalities. All are better tolerated, safer, more acceptable to the patient, and are less expensive than a liver biopsy. Biomarkers have various advantages like minimally invasive, easy to apply with great availability and easier reproducibility, useful for monitoring therapy and less expensive. But then, direct biomarkers involved in extracellular matrix turnover need further validation in different geographic population and indirect biomarkers may not predict early pathophysiological changes in liver parenchyma. The accuracy and diagnostic value of most, if not all, of these biomarkers remain controversial. Hence, there is a need for a biomarker that is specific for the liver and can identify the magnitude of the clinical outcome of the disease. In this review, we discuss the clinical utility, limitations, and development of noninvasive biomarkers in their use as diagnostic and prognostic tests and analyze whether the present known serum biomarkers are laudable and accurate tools for the diagnosis of liver diseases.

Cyclin-Dependent Kinases (CDKs) are a family of enzymes that, along with their Cyclin partners, play a crucial role in cell cycle regulation at many biological functions such as proliferation, differentiation, DNA repair, and apoptosis. Thus, they are tightly regulated by a number of inhibitory and activating enzymes. Deregulation of these kinases’ activity either by amplification, overexpression or mutation of CDKs or Cyclins leads to uncontrolled proliferation of cancer cells. Hyperactivity of these kinases has been reported in a wide variety of human cancers. Hence, CDKs have been established as one of the most attractive pharmacological targets in the development of promising anticancer drugs. The elucidated structural features and the well-characterized molecular mechanisms of CDKs have been the guide in designing inhibitors to these kinases. Yet, they remain a challenging therapeutic class as they share conserved structure similarity in their active site. Several inhibitors have been discovered from natural sources or identified through high throughput screening and rational drug design approaches. Most of these inhibitors target the ATP binding pocket, therefore, they suffer from a number of limitations. Here, a growing number of ATP noncompetitive peptides and small molecules has been reported.

Aim and Objective: Herein, A series of new imidazo[1,2-a]pyridine-chalcone derivatives 3a-m were designed and synthesized to find a new class of antibacterial agents. These compounds were prepared by the aldol condensation of 2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde 2a-b with acetophenone derivatives and other aromatic acetyls. High reaction yields were obtained in a short reaction time, through applying this multi-step pathway. Materials and Methods: In vitro antibacterial activities of the synthesized imidazo[1,2-a]pyridinechalcones were measured against S. aureus, B. subtilis and E. coli with MIC values of 32 -128 μg/mL. Finally, essential structural analyses such as CHN and NMR spectroscopies were used to identify the synthesized chalcones based on imidazo[1,2-a]pyridine derivatives. Results: The results showed that most of the products presented moderate to good antibacterial activities. Compounds 3b, 3d, 3g, 3l and 3m revealed obvious potency against S. aureus, B. subtilis and E. coli with MIC values of 32 μg/mL and 64 μg/mL, which were better when compared with other chalcones. Conclusion: The synthesized antibacterial compounds were obtained with appealing advantages such as high purity, simple pathway, good to excellent yields, inexpensive and easy availability of materials as well as good activities against bacteria. So in this work, a new class of antibacterial chalcones based on imidazo[1,2-a]pyridine has been reported.

Background: Sulfamerazine, a sulfonamide, has been routinely used to treat various bacterial infections, namely Pneumonia, Urinary tract infections, Shigellosis, Bronchitis, Prostatitis, and many more. It interferes with the bacterial folic acid biosynthesis, albeit higher eukaryotes are not susceptible to its action due to the inherent absence of this specific pathway. Objective: In spite of its constant use, Sulfamerazine administration evokes serious issues like the development of antibacterial resistance through environmental contamination, although how it affects the eukaryotic system, specifically its target identification, has not been addressed in detail. Methods: The source of the cell line, including when and from where it was obtained. Whether the cell line has recently been authenticated and by what method. Whether the cell line has recently been tested for mycoplasma contamination. Hela Cells are cultured as per the standard method, amylase and lactate dehydrogenase assay are conducted using a standard procedure with a spectrophotometer. Binding thermodynamics and conformational study have been estimated with isothermal titration calorimetry as well as with docking. Results: Experimental observations reveal that Sulfamerazine inhibits porcine pancreatic amylase in a noncompetitive mode (IC50 of 0.96 mM). The binding of the drug to porcine pancreatic amylase is entropy-driven with conformational changes of the protein as indicated by concomitant redshift. It enhances the inhibitory effects of acarbose and cetapin on their in vitro pancreatic amylase activity. It augments lipid peroxidation and promotes lactic acidosis in a dose-dependent manner. Docking studies ensure effective interactions between Sulfamerazine and proteins like lactic dehydrogenase and porcine pancreatic amylase. Conclusion: Detailed study is to be conducted to confirm whether the molecular scaffold of Sulfamerazine might serve as an effective repurposed drug acting as a lead molecule to design antidiabetic drugs of future use. Alternatively, it should be prescribed with caution under specific medical situations like diabetes, cancer and hepatic disorders manifesting lactic acidosis to avoid the crisis.

Background: Internet browsing has become an indispensable part of day-to-day life. Computers and the internet have occupied almost all sectors of human life. However, it is an artificial source of electromagnetic radiation, which has adverse effects on all living things in dose-dependant manner. Objective: To understand the impact of electromagnetic radiations on plant, Capsicum annuum L. var. Pusa jwala emitted by Wi-Fi routers. Methods: For the germination experiment, Chilli seeds were kept in close vicinity (5 cm) of a Wi-- Fi router for 10 days. For growth and biochemical analysis, different growth and biochemical attributes were studied after 21 days of exposure. Control seeds/plants were kept in another room with almost identical conditions like light, temperature, etc. Plant growth was measured in terms of fresh weight, shoot length, root length, leaf length, leaf breadth and leaf area index. In Biochemical analysis, chlorophyll-a, chlorophyll-b, total chlorophyll, soluble protein, lipid peroxidation and proline contents were measured as per standard protocols. Results: The seed germination in the vicinity of the Wi-Fi router was reduced to 75% and other growth-related parameters like root and shoot length, leaf length, leaf width, leaf area index and fresh weight were significantly reduced. In the biochemical analysis, chlorophyll pigments (Chl. a, b and total chlorophyll) were observed to be reduced by 4.8, 7.2 and 5.7 fold, respectively and protein content reduced by 1.5 fold under the influence of electromagnetic radiations. The product of lipid peroxidation (malondialdehyde) (18 fold) and proline content (10 fold) was found to be increased synergistically. Conclusions: The electromagnetic radiations emitted by the Wi-Fi router have a negative influence on the growth and biochemical responses in Chilli plants.

Background: Hepatocellular Carcinoma (HCC) is the fifth most frequent cancer worldwide with a low overall survival due to high metastasis and recurrence rates. The aim of this study is to assess and compare the possible anti-neoplastic effect of capsaicin and nanoformulated capsaicin on in vitro HCC human cell line HepG2. The source of the cell line, including when and from where it was obtained. Whether the cell line has recently been authenticated and by what method. Whether the cell line has recently been tested for mycoplasma contamination. Materials and Methods: Capsaicin-loaded Trimethyl Chitosan Nanoparticles (CL TMCS NPs) were synthesized by ionotropic gelation of cationic TMCS with capsaicin. The synthesized nanoparticles were characterized through TEM, and zeta analyzer. Human hepatocarcinoma HepG2 cell lines were cultured and treated with 50, 75 & 100 μM of Capsaicin (CAP), plain TMCS NPs and CL-NPs as well as ethanol (control) for 24h and 48h. The induced effects were investigated by flow cytometry, immunocytochemistry assay for Bcl-2, Bax, and caspase proteins and evaluating gene expression levels of Bcl-2, Bax, and MDR-1 mRNA by real-time PCR. Results: Our results demonstrated that capsaicin- loaded NPs had the potential to significantly increase capsaicin bioactivity compared with the plain capsaicin formulation either in inducing apoptosis through altering expression of apoptotic regulators or modifying MDR-1 expression. Conclusions: TMCs nanoparticles investigated in this study may be a good drug delivery vehicle for capsaicin. Application of capsaicin-loaded NPs in HCC management as an adjunct therapeutic approach may be a novel strategy to improve the treatment efficacy and resistance of the conventionally used chemotherapy.