Current Chemical Biology - Volume 11, Issue 2, 2017

Abstract: Background: Iron-sulfur clusters are inorganic prosthetic groups composed of only iron and inorganic sulfur atoms. Organisms develop different pathways to sense their local environment and to respond and adapt to changes. Objective: We focused on Fe-S-containing proteins, which control their activity in response to redox signals by changing the redox state of their cluster. Result: When reduced, these Fe-S cluster-containing sensors are all inactive. As soon as their cluster perceives a signal that induces its oxidation, they switch to an « active state ». Conclusion: This sensing mechanism efficiently helps cells to turn on survival pathways quickly and recover from stressful conditions.

Background: Enzymes efficiently catalyze various specific biochemical and biological reactions. Researchers seem to be playing around these biomolecules to get answers to some imperative questions like molecular evolution, crucial residues in binding with substrate, cofactor specificity etc. Molecular evolution of enzymes enables researchers to deduce the evolutionary history of different organisms via comparison of protein sequences. Neutral theory of molecular evolution predicted that silent sites in protein coding regions evolve faster than replacement sites (due to different functional constraints) and the amount of sequence divergence correlates with the level of heterozygosity. Objective: Artificially redesign active site of enzymes that can alter its properties like efficiency, thermal stability and specificity using different directed molecular evolution techniques. Conclusion: In this article, we have tried to bring all innovative works together which would be beneficial in the field of enzyme engineering, industry as well as therapeutics.

Background: The present investigation describes all the peptides (labaditin, biobollein, curcacycline A, podacycline A, podacycline B, cyclogossine A, cyclogossine B, curcacycline B, chevalierin A, chevalierin B, chevalierin C, pohlianin A, pohlianin B, pohlianin C, mahafacyclin A, mahafacyclin B, integerrimide A, integerrimide B, JCpep7, jatrophidin, ribifolin and unnamed) isolated from the Jatropha genus reported during the last three decades in the scientific literature. Objective: To discuss the state of art of peptides belonging to Jatropha genus. Method: This report covers a joint analysis of taxonomy, botanical distribution, usage, isolation, homology, biological function and structural information of all Jatropha genus peptides. Results: It provides an up-to-date list of Jatropha genus peptides that are currently available in the literature, to facilitate and guide new strategies as well as to encourage the next generation of plant peptide researchers in this promising field. Conclusion: Even though structural elucidation, interaction mechanisms, biosynthesis and posttranslational modifications remain challenges that need to be overcome, there is little doubt that novel peptide findings will elucidate these questions and that their synthetic analogues will represent a promising future for developing therapeutic drugs.

Background: Extensive research in the last decade has clearly shown the close relationship between dietary habits, food intake, and gene expression, which is also determined by the action of dietary compounds on chromatin regulation. Objective: Epigenetic modifications are referred to the change in gene expression without changing in DNA sequence. Methods: Recent studies revealed that epigenetic modulations such as DNA methylation, histone modification (acetylation, methylation, and phosphorylation), and chromatin remodeling provide significant contributions to the development of human diseases, including obesity and Type 2 diabetes. Moreover, epigenetic information from the intrauterine and early developmental environments also contributes to the adult metabolic states in both humans and mice. Results: There is accumulating evidence for a role for epigenetic changes in the process of metabolic memory and diabetes-associated complications. Nutrient-induced chromatin epigenetic changes via DNA methylation and histone post-translational modifications, significantly contribute to metabolic regulation. Conclusion: In this review we will focus on how dietary components which are widely present in daily dietary, acting on epigenetic mechanisms, may exhibit various effects on metabolic diseases.

Background: Given the important role of GABA in the central nervous system, the nootropic-neuroprotective activity of aniracetam, a cyclised derivative of GABA, the participation of inflammation and oxidative stress in degenerative disorders, some novel compounds combining the above characteristics are studied. Objectives: A series of amides of GABA with the antioxidant acids lipoic acid, 3,5-di-tert-butyl-4- hydroxybenzoic acid, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid and trolox, their ethyl or methyl esters and their cyclised N-acyl-pyrrolidin-2-ones have been prepared as antioxidants, possible nootropics aniracetam related structures. Results: The most potent antioxidant was (R)-1-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carbonyl) pyrrolidin-2-one (11), which was found to inhibit the ferrous/ascorbate induced lipid peroxidation of microsomal membrane lipids, with IC50 13 μM. The majority of the tested compounds inhibited cyclooxygenases (18-72%); 1-(3,5-di-tert-butyl-4-hydroxybenzoyl)pyrrolidin-2-one (6), (E)-methyl 4-(3- (3,5-di-tert-butyl-4-hydroxyphenyl)acrylamido)butanoate (8) and (R)-ethyl 4-(6-hydroxy-2,5,7,8- tetramethylchroman-2-carboxamido)butanoate (10), which are potent inhibitors of soybean lipoxygenase, having IC50 value 47-48 μM. They reduced carrageenan-induced rat paw oedema by 41-62%. Conclusion: Since inflammation and oxidative stress are common characteristics of degenerative disorders, agents combining anti-inflammatory, antioxidant and cytoprotective properties could be proven useful for their treatment.

Background: Mycobacterium tuberculosis (M. tuberculosis), has a long history of association with human life. By evading the immune response it survives inside macrophages as most successful pathogens known today. An important virulence factors for pathogenic mycobacteria has recently been identified to be a eukaryotic-like serine/threonine protein kinase, termed protein kinase G (PknG). Objective: In this connection, the drug target PknG was identified by using KEGG database and network analysis through Cytoscape software. Inhibition of PknG activity leads to a rapid degradation of mycobacteria inside host cells. In this study, eight novel thiazolo [2,3-b] quinazolin-3-phenyl hydrazone (5a-h) derivatives were synthesized and have been docked to the active site of the PknG using Auto- Dock 4.2 program. Method: The free energies of binding (ΔG) and inhibition constants (Ki) of the docked compounds were calculated by the Lamarckian Genetic Algorithm (LGA). Results: These values suggest that compounds 5f, 5c, 5a are excellent inhibitors of PknG, these compounds interact with lysine 181which was a key residue for PknG activity and the synthesized compounds were also screened by in vitro BACTEC 460 radiometric method against M. tuberculosis H37Rv strain at 6.25 μg/mL. Conclusion: The highest inhibition observed with the synthesized compound was 6,7,8,9-tetrahydro- 5H-5-(2'-hydroxyphenyl)-2-(4'-fluorobenzylidene) thiazolo[2,3-b]quinazolin-3-phenylhydrazone 5f.

Objective: In previous studies, we evaluated antibacterial activity of CM11 peptide against multiple drug resistant clinical isolates of six bacteria species, alone and in combination with conventional antibiotics. Although antimicrobial peptides like CM11 peptide are one of the best new alternative antibiotics, the side effects such as toxicity are major problem. Previously the in vitro cytotoxic effects of the peptide, viability of some cell lines have been investigated. Methods: For in vivo studies, the present study is conducted to obtain more clarification about the toxicity and histopathological effects of peptide in mice. For this purpose three groups of mice were treated with different concentrations (0.2, 2.5, and 7.5 mg/kg) of peptide and then histological study for the liver, kidney and jejunum and aspartate and alanine aminotransferase activities and total serum bilirubin and albuminin blood plasma levels were measured. Results: Our study showed that the activities of aminotransferase, also total serum bilirubin and albumin levels were not significantly increased while different histological changes were observed in organs’ tissue. These changes were dependent on peptide concentration so that an increase in focal inflammation was observed with increasing peptide concentration; however these histological changes are not considerable in lower concentration. Conclusion: Our findings showed that although in comparison with the control group, markers level is normal but damages were visible in the tissues, as increase in the level of tissue damages has not led to increased levels of markers. It seems that the lack of correlation between tissue damage and level of liver markers probably is related to the level of damage.