Hydrogen sulfide (H2S) is a novel type signaling molecule in plants Seed germination is a key stage of life cycle of plants, which is vulnerable to environmental stress including high temperature However, under high temperature stress, whether pre-soaking of maize seeds with NaHS (a H2S donor) could improve seed germination and seedling growth and the possible mechanisms are not completely clear In this study, maize seeds pre-soaked with NaHS enhanced germination percentage, sprout length, root length, and fresh weight compared with the control without NaHS treatment, illustrating that H2S could improve maize seed germination and seedling growth under high temperature In addition, in comparison to the control, NaHS pre-soaking stimulated antioxidant enzymes [ascorbate peroxidase (APX), glutathione reductase (GR), guaiacol peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT)] activities and the contents of water soluble non-enzymatic antioxidants [ascorbic acid (AsA) and glutathione (GSH)], as well as the ratio of reduced antioxidant to oxidized antioxidant Moreover, pre-soaking with NaHS activated Δ1-pyrroline-5-carboxylate synthetase (P5CS) and ornithine aminotransferase [OAT; both are rate-limiting enzymes in proline (Pro) synthesis], betaine aldehyde dehydrogenase [BADH; a key enzyme in glycine betaine (GB)], and trehalose (Tre)-6-phosphate phosphatase (a key step in Tre synthesis), which in turn accumulated Pro, GB, and Tre in germinating seeds compared with the control Also, an improved germination by NaHS under high temperature was reinforced by the above osmotic adjustment substances (osmolytes) alone, while deteriorated by the inhibitors of osmolyte biosynthesis [gabaculine (GAB), disulfiram (DSF), and sodium citrate (SC)] These results imply that H2S could improve maize seed germination and seedling growth under high temperature by inducing antioxidant system and osmolyte biosynthesis

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Signaling Molecule Hydrogen Sulfide Improves Seed Germination and Seedling Growth of Maize (Zea mays L.) Under High Temperature by Inducing Antioxidant System and Osmolyte Biosynthesis.

The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer diseases have been a serious clinical problem around the world for over 50 years. Therefore, intense searching of new leading structures and active substances, which may be used as new drugs, especially against strain resistant to all available therapeutics, is very important. Dihydrofolate reductase (DHFR) has attracted a lot of attention as a molecular target for bacterial resistance over several decades, resulting in a number of useful agents. Trimethoprim (TMP), (2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine) is the well-known dihydrofolate reductase inhibitor and one of the standard antibiotics used in urinary tract infections (UTIs). This review highlights advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors. In addition, this report presents the differences in the active site of human and pathogen DHFR. Moreover, an excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented.

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Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.

Hydrazonoyl bromide precursors as DHFR inhibitors for the synthesis of bis-thiazolyl pyrazole derivatives; antimicrobial activities, antibiofilm, and drug combination studies against MRSA.

Osmolytes resist against harsh osmolarity: Something old something new.

A new series of trimethoprim (TMP) analogs containing amide bonds (1–6) have been synthesized. Molecular docking, as well as dihydrofolate reductase (DHFR) inhibition assay were used to confirm their affinity to bind dihydrofolate reductase enzyme. Data from the ethidium displacement test showed their DNA-binding capacity. Tests confirming the possibility of DNA binding in a minor groove as well as determination of the association constants were performed using calf thymus DNA, T4 coliphage DNA, poly (dA-dT)2 and poly (dG-dC)2. Additionally, the mechanism of action of the new compounds was studied. In conclusion, some of our new analogs inhibited DHFR activity more strongly than TMP did, which confirms, that the addition of amide bonds into the analogs of TMP increases their affinity towards DHFR.

https://www.mdpi.com/1420-3049/25/1/116/pdf

Trimethoprim: An Old Antibacterial Drug as a Template to Search for New Targets. Synthesis, Biological Activity and Molecular Modeling Study of Novel Trimethoprim Analogs.

Osmolyte induced enhancement of expression and solubility of human dihydrofolate reductase: An in vivo study.

Dihydrofolate reductase is one of the important enzymes for thymidylate and purine synthesis. It has been used as a drug target for treatment of various diseases. A large number of pharmaceutical drugs have been designed to inhibit the activity of dihydrofolate reductase. However, over the period of time some organisms have developed resistance against some of these drugs. There is also a chance of cross reactivity for these drugs, as they may target the dihydrofolate reductase enzyme of other organisms. Although using NMR spectroscopy, phylogenetic sequence analysis, comparative sequence analysis between dihydrofolate enzymes of various organisms and molecular modeling studies, a lot has been unraveled about the difference in the structure of this enzyme in various organisms, yet there is a need for deeper understanding of these differences so as to design drugs that are specific to their targets and reduce the chance for cross reactivity. The dihydrofolate enzyme can also be explored for treatment of various other diseases that are associated with the folate cycle. Keywords : Dihydrofolate Reductase; Drug target; Inhibitor; Folate cycle; NADPH

Dihydrofolate reductase as a versatile drug target in healthcare

Quantification of differential efficacy of chemical chaperones in ameliorating solubilization and folding of zebrafish dihydrofolate reductase.

The proper functioning of organisms in stress conditions is an axiological exercise Proteins are vulnerable to denaturation and misfolding under hiked temperatures, increased hydrostatic pressure, the presence of chaotropic agents, etc Osmolytes are one of the most important groups of molecules that are employed by the cell as an adaptation to these harsh conditions These small molecules maintain cell volume, osmotic equilibrium, redox states, and energy quanta of the cell The current chapter reviews the versatility of the osmolytes in various metabolic functions and how widely they are distributed across the different classes of organisms (plants, animals, insects, marine animals, etc) This chapter discusses their diversity and the exact mechanism by virtue of which these osmolytes are able to impart stability to the proteins It also elucidates on the application of these osmolytes in treatment of various diseases and as possible drugs from the pharmaceutical point of view

Naira Rashid

Papers

Osmolyte induced enhancement of expression and solubility of human dihydrofolate reductase: An in vivo study.

Dihydrofolate reductase as a versatile drug target in healthcare

Quantification of differential efficacy of chemical chaperones in ameliorating solubilization and folding of zebrafish dihydrofolate reductase.

Osmolyte System and Its Biological Significance

Kinetics and thermodynamics of the thermal inactivation and chaperone assisted folding of zebrafish dihydrofolate reductase