Background: A series of bis(indolyl)methanes (3a-3o) have been synthesized using a greener and new approach using the reaction of different substituted aldehydes and indole in the presence of an easily available and biodegradable base such as piperidine in acetic acid at room temperature and characterized with UV (Ultraviolet-visible spectroscopy), Gas Chromatography-Mass Spectrometry (GCMS), Proton Nuclear Magnetic Resonance (H-NMR), and Fourier Transform Infrared Spectroscopy (FTIR). Methods: All 15 newly synthesized compounds (3a-3o) were subjected to in-vitro anti-microbial activity determination and compared with the known standard drug ciprofloxacin (1-2 μg/mL). Our in-silico analysis on the target protein, pdb id: 1d7u suggested that these analogues would be highly active against bacterial targets and thus, would act as good antimicrobial agents. Results: All 15 newly synthesized compounds (3a-3o) displayed potent activity on various experimental microbial strains (1.0-1.4 μg/mL). Compound, 3k was obtained as the best docked compound against common bacterial target enzyme, (pdb id:1d7u). The standard, Ciprofloxacin, retained the docking score of -111.3 Kcal/mol with similar binding amino acid residues (LYS272 (Pi-cation); ALA A:245 (Pisigma); TRP A:138 (Pi-Pi); ALA A:112; and MET A:141 (Pi-alkyl)) as of inbound. Conclusion : We believe that our current study would shed more light on the development of potent bis(indolyl)methanes as antimicrobial agents.

Background: Plants are a main source of drugs for the therapy of a large number of diseases. Objective: The aim of the present work is to evaluate the in vitro antioxidant and anti-α-amylase and anti-peroxidases (HPR) potentials of phenolic extracts obtained from three spontaneous plants; growing in the South of Algeria such as (Chamomilla pubescens, Pulicaria crispa, and Rhanterium adpressum). This is the first report on the study of α-amylase and horseradish peroxidase (HRP) inhibitory activity for phenolic extracts from the Chamomilla pubescens and Pulicaria crispa plants. Method: The antioxidant activity was evaluated in vitro using four tests: DPPH, CUPRAC, FRAP, and ABTS. The phenolic, flavonoid, and tannin compounds of the three selected Algerian plants were quantified. Also, the inhibition of α-amylase and HRP was evaluated. Results: The quantification of the total phenolic contents revealed that they are widely variable, and depending on extraction solvents, the highest content was recorded by the ethyl acetate extract of Chamomilla pubescens (flowers) 774.93±60.14mg/100 g of dry matter. In all the antioxidant tests, ethyl acetate extracts showed the most effective activity, which the best was (VCEAC = 65.62 ±0.50 µM/g dry matter) of Pulicaria crispa for the DPPH test. Furthermore, the results of α-amylase and peroxidase inhibitory effects indicated that all plants extracts have inhibitory effects on the two enzymes, with AEIC values ranged from 76.55±3.54 to 149.54±6.68 μM/g of dry matter for the α-amylase, and CEIC values ranged from 8.89±2.22 to 9668.31±254.42 μM/g of dry matter for the peroxidase (HRP). Conclusion: The present study results suggest that the three Algerian spontaneous plant species (Rhanterium adpressum, Pulicaria crispa, and Chamomilla pubescens) inhibit peroxidase and α-amylase and exhibit a high antioxidant activity what can be related to the treatment of diabetes and thyroid diseases.

Background: Obesity is a growing global health problem. Obesity leads to cardiovascular disorders, musculoskeletal disorders, diabetes, and certain types of cancer. One of the approaches to controlling and treating obesity has involved inhibition of dietary lipid digestion by pancreatic lipase inhibitors. Microbes and plant sources provide a rich source of enzyme inhibitors, including pancreatic lipase inhibitors that can be developed as a drug for obesity treatment. Objective: The objective of the work, mainly focuses and highlights the isolation of actinomycetes and screening for pancreatic lipase inhibitors production. Methods: Actinomycetes were isolated from soil samples by pre-treatment of samples and using selective growth medium with and without antibiotics. Isolated actinomycetes were grown in fermentation conditions and metabolites were extracted with isopropyl alcohol and the solvent evaporated to get crude material. Extract of each isolate screened for pancreatic lipase inhibition using p- nitrophenyl palmitate as substrate by spectroscopic method. Results: A total of 86 actinomycetes strains were isolated from soil samples. Out of 86 extracts,10 extracts have shown positive results for porcine pancreatic lipase inhibition, and inhibition activity was in the range of 10-80%. 50 % inhibitory concentration determined using 1 to 8 mg/mL extract in the assay. Extract of isolate A9, B3, and C6 having 50 % inhibitory activity below 3 mg/mL concentration and Orlistat as a standard has shown 50 % inhibitory activity at below 1 mg/mL concentration. Conclusion: The results conclude that actinomycetes are potential source of lipase inhibitors, which may lead to valuable novel drugs for obesity treatment.

Background and Aim: This study aims to alleviate the microbiologically affected corrosion that occurred by sulfate-reducing bacteria (SRB) through synthesizing a bio-based polyurethane polymer and its nanocomposite coating, silver nanoparticles (PU-Ag). Moreover, it will also evaluate the effect of PU alone and PU-Ag as inhibitors for adenylyl sulfate reductase (APS), the main enzyme for sulfate reduction. Methods: In this study, the PU was prepared from vegetable soybean oil, and the silver nanoparticles (Ag-NPs) with a concentration of 1% were coated to the PU forming a nanocomposite. The PU and the PU-Ag were characterized and evaluated as inhibitors of the APS reductase enzyme. Results: The results obtained from FTIR, UV, DLS, TEM, and XRD confirmed the preparation structure of the PU and PU-Ag. Furthermore, the PU/PU-Ag competitively inhibited the APS reductase with an inhibition constant equal to 35.7 and 11 mg, respectively. These indicated the exerted inhibitory effect of PU/PU-Ag upon the activity of the APS reductase enzyme. Conclusion: The APS reductase enzyme produced by SRB, which is recorded as a big problem in the oil and gas industry such as pitting corrosion of tanks and pipelines, could be inhibited by PU and PU-Ag.

Background: Inhibition of α-amylase and α-glucosidase is considered as an important therapeutic target to manage type 2 diabetes mellitus (T2DM), reducing postprandial hyperglycemia (PPHG). Objective: The present work explored the antidiabetic activities of five artificial food colorings by α- amylase and α-glucosidase enzyme inhibition in vitro and in Silico. Methods: In this study, inhibition of α-amylase and α-glucosidase was evaluated. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (food colorings) was followed by QSAR and molecular docking studies. Results: The in vitro results obtained show that the blue patent (SIN131) exhibited more potent inhibition with IC50 values of 0.03± 0.01 mM and 0.014±0.001 mM against α-amylase and α-glucosidase inhibition respectively compared to acarbose. The QSAR study found a strong correlation between IC50 values with four molecular descriptors. This linear regression confirms that a strong polarity (Apol) and low hydrophobia (ALogP) favor the inhibitory effect of these colorings toward both enzymes. Also, a negative role of the number of heavy atoms has been demonstrated in the phenomenon of inhibition of this enzyme. Finally, the descriptor εlumo (electronic affinity) plays a crucial role on the inhibitory power of these dyes toward both enzymes by electron transfer. The virtual screening of the inhibition of α-amylase and α-glucosidase by these colorings, using Molegro Virtual Docker (MVD), allowed us to obtain stable complexes with interaction energies resulting from the place of hydrogen bonds and several hydrophobic interactions. However, the sulfonate groups of these colorings can be the major factors in the inhibition of these enzymes. On the other hand, Rerank Score with the pose are perfectly correlated (R2> 0.76) to the inhibitory activity of these food colorings measured experimentally. Conclusion: The present study suggests that the Blue Patent V (SIN131) effectively acts as α-amylase and α-glucosidase inhibitor leading to a reduction in starch hydrolysis and eventually to lower glucose levels.

Introduction: Coronaviruses constitute the subfamily Orthocoronavirinae, in the Coronaviridae family. Those viruses are a positive-sense and very long single-stranded RNA viruses. Infection- related to SARS CoV2 was named as a pandemic disease by the World Health Organization on Mars 4, 2020. Aim and Objective: The objective of this work is the identification of potential vaccine targets of SARS CoV2. We aim to provide the potential therapeutic target that can inhibit the spread of virus and identify miRNAs, and reminding proposals to improving the effectiveness of these vaccines. Methods: Several clinical trials have been stated to design the management process against this pathology and the most proposed drugs have been commercialized for other viral pathologies. Thus, no specific therapeutic protocol has been established. Results: Our result showed that the potential molecules may specific region in the viral ARN and exert an inhibitor activity against the viral transcription. Conclusion: We conclude throughout our results that several potential therapeutic targets can act at different stages of the viral life cycle by identifying siRNA interfering with molecules that may inhibit viral replication.

Background: Alzheimer's disease (AD) is an unexplained progressive degenerative brain disease; it accounts for 60-70% of dementia cases worldwide, has an estimated global incidence of 24.3 million, and is associated with deterioration of the central nervous system. Acetylcholinesterase (AChE) is an enzyme that catalyzes the breakdown of acetylcholine to acetate and choline. It is also the potential target of most of the clinically used drugs for the treatment of AD. The degeneration of cholinergic neurons and the loss of neural transmission are the main reasons for the decline of cognitive ability in AD patients. Objective: In recent years, the development of targeted drugs in AD has made significant achievements. The global impact of AD continues to grow, and as a result, the focus of disease-modifying therapies remains elusive. The role of treatment is not limited to pharmacology but involves many factors, such as the psychological, social, and economic aspects of the patient and family. AChE is an important target in AD to consider the use of AChE inhibitors in patients with mild to moderate AD, even though the costs are high and no other direct progress has been made. Although there are many AChE inhibitors, there is no selective potent inhibitor for AChE. There is still a need to address human AChE structure, provide key insights into key protein-ligand interactions, and provide the basis for molecular modeling and structure-based drug design. Conclusion: In this review, we briefly introduce the clinical characteristics of AD, the development of crystal structure, and the latest research on AD. In recent years, the development of different strategies for amyloid-β, BACE1, and type-1 interferon receptor alpha-1 has attracted great attention. There is an urgent need to further characterize available instrumental compounds to explore the use of new selectivity and key protein-ligand interactions in AD. In the past few decades, great progress has been made in the treatment of AD, but AD is still one of the world's problems, and the inability to cure AD, indicates that there is an urgent need for new treatments.

Background: Diabetes mellitus (DM) is an important global health problem especially in developed countries and insufficient lifestyle induces this phenomenon. Finding efficient treatment for DM is an interesting goal for researchers. Objective: Herein we tried to design and synthesize a series of quinazoline derivatives and investigate their bioactivity as possible α-Glucosidase inhibitor agents. Method: Compounds 1-14 were synthesized using a multicomponent reaction. 1HNMR, 13C NMR, MS, and IR spectroscopy were used for the characterization of synthesized compounds. α- Glucosidase inhibitory activity of compounds 1-14 was evaluated using p-nitrophenyl‐α‐Dglucopyranoside (pNPG) as a substrate of the α-glucosidase enzyme (EC3.2.1.20, Saccharomyces cerevisiae). The mechanism of inhibition of the α-glucosidase enzyme was investigated using kinetic studies. Molecular docking was also done using autodock software to find the possible mode of interaction of compound 8 and the enzyme active site. Results: Most of the tested compounds showed higher activity in inhibition of the enzyme in comparison to the standard, acarbose. Compound 8 exerted the best activity with the IC50 value of 291.5 μM. A kinetic study indicated a competitive inhibition of the α-glucosidase enzyme by compound 8. Finally, docking studies showed the interactions between compound 8 and enzyme active site residues. Conclusion: 2,4-Diarylquinazoline scaffold has good antidiabetic activity, so it is interesting to synthesize more 2,4-diarylquinazoline derivatives and evaluate their antidiabetic activities.

Prostate cancer is one of the prominent death cause in males with alarming rates of inclusion of new cases each year. There are many new classes of anti-tumor agents already investigated that modulate the epigenetic or non-epigenetic mechanisms such as cell cycle arrest, apoptosis, cell death within cancer cells. Histone deacetylase (HDAC) inhibitors are one of them. In recent times, the use of HADC inhibitors are approved as a clinical molecule to treat a group of malignancies. Vorinostat and depsipeptide are two new HDAC inhibitors that are approved by the Food and Drug Administration. The present review is an effort to summarize the recent findings related to HDAC inhibitors against prostate cancer along with their molecular mechanism and biological mode of actions behind the anticancer efficacy.