Design, Synthesis and Antifungal Activity of Stapled Aurein1.2 Peptides

Aurein1.2 is a 13-residue antimicrobial peptide secreted by the Australian tree frog Litoria aurea. In order to improve its stabilities, the helical contents and corresponding biological activities of Aurein1.2 (a series of stapled analogues) were synthesized, and their potential antifungal activities were evaluated. Not surprisingly, the stapled Aurein1.2 peptides showed higher proteolytic stability and helicity than the linear counterpart. The minimum inhibitory concentration (MIC) of ten stapled peptides against six strains of common pathogenic fungi was determined by the microscale broth dilution method recommended by CLSI. Of them, Sau-1, Sau-2, Sau-5, and Sau-9 exhibited better inhibitory effects on the fungi than the linear peptide. These stapled Aurein1.2 peptides may serve as the leading compounds for further optimization and antifungal therapy.

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Design, synthesis, and biological activities of novel thiophene, pyrimidine, pyrazole, pyridine, coumarin and isoxazole: Dydrogesterone derivatives as antitumor agents

Open Chemistry ◽

10.1515/chem-2021-0028 ◽

2021 ◽

Vol 19 (1) ◽

pp. 322-337

Author(s):

Karam A. El-Sharkawy ◽

Mohammed Al Bratty ◽

Hassan A. Alhazmi ◽

Asim Najmi

Keyword(s):

Elemental Sulfur ◽

Antitumor Agents ◽

Biological Activities ◽

Hydroxylamine Hydrochloride ◽

Inhibitory Effects ◽

Antitumor Activities ◽

Design Synthesis ◽

H Nmr ◽

Growth Inhibitory ◽

Thiophene Derivatives

Abstract On the basis of our consideration to design and to develop antitumor activities of heterocyclic compound derivatives, especially in fused ring system, we refer to the possibility of the heterocyclic extension of one of the most important steroid compounds used as a medicinal drug. The reaction of dydrogesterone with each of the malononitrile or ethylcyanoacetate containing elemental sulfur afforded thiophene derivatives 1a,b. Also, dydrogesterone was reacted with a mixture of ethylcyanoacetate–hydrazine, ethylcyanoacetae–urea, or ethylcyanoacetate–thiourea to produce pyrazole derivative 4 and pyrimidine derivatives 5a,b. Thienopyrimidine derivatives 2a–d were introduced from the reaction of thiophene derivatives 1a,b with either phenylisothiocyanate or benzoylisothioyanate. Furthermore, compounds 1a,b were directed toward the reaction with ethylcyanoacetate to produce compounds 6a,b, and the last compounds 6a,b were directed toward cyclization to obtain thienopyridine derivatives 7a,b. In addition, compounds 6a,b were subjected to react with different carbonyl compounds, such as salicylaldehyde, cyclopentanone-elemental sulfur, malonaldehyde, and acetylacetone to produce coumarin derivatives 8a,b, fused thiophene derivatives 9a,b, and pyridine derivatives 10a–d. Isooxazole derivatives 12a,b were afforded through the reaction of compounds 6a,b with hydroxylamine hydrochloride. Finally, 2-pyridone derivatives 14a,b were obtained through the reaction of compounds 6a,b with benzoylacetonitrile. Conformation structure of the synthesized compounds was established by applying IR, 1H NMR, 13C NMR, and mass spectrometry, and their antitumor activity was examined. Some compounds showed promising growth inhibitory effects on the three different cell lines.

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Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200302114620 ◽

2020 ◽

Vol 20 (10) ◽

pp. 908-920 ◽

Cited By ~ 2

Author(s):

Su-Min Wu ◽

Xiao-Yang Qiu ◽

Shu-Juan Liu ◽

Juan Sun

Keyword(s):

Monoamine Oxidase ◽

Heterocyclic Compounds ◽

Biological Activities ◽

The Past ◽

Structure Activity ◽

Receptor Interactions ◽

Heterocyclic Derivatives ◽

Inhibitory Activities ◽

Leading Compounds ◽

Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

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Design, Synthesis and Pharmacological Evaluation of Novel Antiinflammatory and Analgesic O-Benzyloxime Compounds Derived From Natural Eugenol

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180620145609 ◽

2019 ◽

Vol 16 (10) ◽

pp. 1157-1166

Author(s):

Rodrigo César da Silva ◽

Fabiano Veiga ◽

Fabiana Cardoso Vilela ◽

André Victor Pereira ◽

Thayssa Tavares da Silva Cunha ◽

...

Keyword(s):

Formalin Test ◽

Docking Studies ◽

Paw Edema ◽

Inhibitory Effects ◽

Structural Pattern ◽

Design Synthesis ◽

Drug Candidates ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Cox 1

Background: : A new series of O-benzyloximes derived from eugenol was synthesized and was evaluated for its antinociceptive and anti-inflammatory properties. Methods: : The target compounds were obtained in good global 25-28% yields over 6 steps, which led us to identify compounds (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-(4- (methylthio)benzyloxime (8b), (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- bromobenzyloxime (8d) and (Z)-5,6-dimethoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one-O-4- (methylsulfonyl)benzyloxime (8f) as promising bioactive prototypes. Results:: These compounds have significant analgesic and anti-inflammatory effects, as evidenced by formalin-induced mice paw edema and carrageenan-induced mice paw edema tests. In the formalin test, compounds 8b and 8f evidenced both anti-inflammatory and direct analgesic activities and in the carrageenan-induced paw edema, with compounds 8c, 8d, and 8f showing the best inhibitory effects, exceeding the standard drugs indomethacin and celecoxib. Conclusion: : Molecular docking studies have provided additional evidence that the pharmacological profile of these compounds may be related to inhibition of COX enzymes, with slight preference for COX-1. These results led us to identify the new O-benzyloxime ethers 8b, 8d and 8f as orally bioactive prototypes, with a novel structural pattern capable of being explored in further studies aiming at their optimization and development as drug candidates.

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Design, Synthesis and Antifungal Activity of Novel 1-(Adamantan-1-yl) ethanone Oxime Esters

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190329225307 ◽

2020 ◽

Vol 17 (5) ◽

pp. 526-532

Author(s):

Si Liu ◽

Li-Zhi Niu ◽

Yan-Hua Shi ◽

Fu-Xian Wan ◽

Lin Jiang

Keyword(s):

Antifungal Activity ◽

Biological Activities ◽

Lead Compound ◽

Design Synthesis ◽

Antifungal Activities

Background: Oxime compounds, including oxime ethers and oxime esters, possess various biological activities. Many oxime ethers have been widely used in the fields of pesticides and medicines. However, oxime ethers are rarely used in the field of pesticides. Methods: We chose the excellent fungicide pyrifenox as the lead compound, integrated pyridinyl, adamantyl and benzoyl moieties into one molecule, while also designed and synthesized ten 1- (adamantan-1-yl)ethanone oxime esters containing pyridinyl moiety. Moreover, we also evaluated their preliminary antifungal activities against S. sclerotiorum and B. cinerea. Results: The target compounds were characterized by NMR, IR and HRMS. The preliminary bioactivity test showed that they exhibited some antifungal activity to S. sclerotiorum and B. cinerea, and EC50 values were in the range of 14.16-32.97 and 27.60-52.82 μg/mL, respectively. Conclusion: Some target compounds such as 3d, 3e, 3h and 3i, exhibited moderate activities against S. sclerotiorum, with EC50 values of 14.16-18.18 μg/mL.

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Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190319142934 ◽

2019 ◽

Vol 19 (9) ◽

pp. 1132-1140

Author(s):

Heba A.E. Mohamed ◽

Hossa F. Al-Shareef

Keyword(s):

Cell Cycle ◽

Anticancer Agents ◽

Biological Activities ◽

Flow Cytometric Analysis ◽

Annexin V ◽

Cytotoxic Activities ◽

Significant Group ◽

Design Synthesis ◽

Standard Drug ◽

Wide Range

Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.

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Synthesis of Fragments of the Vasoactive Intestinal Peptide (VIP) and Analysis of Their Residual Biological Activities

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19951229 ◽

1995 ◽

Vol 60 (7) ◽

pp. 1229-1235 ◽

Cited By ~ 2

Author(s):

Ivana Zoulíková ◽

Ivan Svoboda ◽

Jiří Velek ◽

Václav Kašička ◽

Jiřina Slaninová ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Residual Activity ◽

Detailed Examination ◽

Amino Acid Residues ◽

Linear Peptide ◽

Zone Electrophoresis ◽

Capillary Zone

The vasoactive intestinal (poly)peptide (VIP) is a linear peptide containing 28 amino acid residues, whose primary structure indicates a low metabolic stability. The following VIP fragments, as potential metabolites, and their analogues were prepared by synthesis on a solid: [His(Dnp)1]VIP(1-10), VIP(11-14), [D-Arg12]VIP(11-14), [Lys(Pac)15,21,Arg20]VIP(15-22), and VIP(23-28). After purification, the peptides were characterized by amino acid analysis, mass spectrometry, RP HPLC, and capillary zone electrophoresis. In some tests, detailed examination of the biological activity of the substances in vivo and in vitro gave evidence of a low, residual activity of some fragments, viz. a depressoric activity in vivo for [His(Dnp)1]VIP(1-10) and a stimulating activity for the release of α-amylase in vitro and in vivo for [Lys(Pac)15,21,Arg20]VIP(15-22) and VIP(23-28).

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Cytokinin N-glucosides: Occurrence, Metabolism and Biological Activities in Plants

Biomolecules ◽

10.3390/biom11010024 ◽

2020 ◽

Vol 11 (1) ◽

pp. 24

Author(s):

Eva Pokorná ◽

Tomáš Hluska ◽

Petr Galuszka ◽

H. Tucker Hallmark ◽

Petre I. Dobrev ◽

...

Keyword(s):

Metabolic Pathways ◽

Growth And Development ◽

Biological Activities ◽

Physiological Effects ◽

Inhibitory Effects ◽

Plant Growth And Development ◽

The Past ◽

Complex Process ◽

Considerable Impact ◽

Physiological Impact

Cytokinins (CKs) are a class of phytohormones affecting many aspects of plant growth and development. In the complex process of CK homeostasis in plants, N-glucosylation represents one of the essential metabolic pathways. Its products, CK N7- and N9-glucosides, have been largely overlooked in the past as irreversible and inactive CK products lacking any relevant physiological impact. In this work, we report a widespread distribution of CK N-glucosides across the plant kingdom proceeding from evolutionary older to younger plants with different proportions between N7- and N9-glucosides in the total CK pool. We show dramatic changes in their profiles as well as in expression levels of the UGT76C1 and UGT76C2 genes during Arabidopsis ontogenesis. We also demonstrate specific physiological effects of CK N-glucosides in CK bioassays including their antisenescent activities, inhibitory effects on root development, and activation of the CK signaling pathway visualized by the CK-responsive YFP reporter line, TCSv2::3XVENUS. Last but not least, we present the considerable impact of CK N7- and N9-glucosides on the expression of CK-related genes in maize and their stimulatory effects on CK oxidase/dehydrogenase activity in oats. Our findings revise the apparent irreversibility and inactivity of CK N7- and N9-glucosides and indicate their involvement in CK evolution while suggesting their unique function(s) in plants.

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Functional design of glycan-conjugated molecules using a chemoenzymatic approach

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab024 ◽

2021 ◽

Author(s):

Makoto Ogata

Keyword(s):

Molecular Weight ◽

Large Scale ◽

Biological Activities ◽

Natural Compounds ◽

Low Molecular Weight ◽

Functional Design ◽

Enzymatic Method ◽

Conjugated Molecules ◽

Design Synthesis ◽

And Function

Abstract Carbohydrates play important and diverse roles in the fundamental processes of life. We have established a method for accurately and a large scale synthesis of functional carbohydrates with diverse properties using a unique enzymatic method. Furthermore, various artificial glycan-conjugated molecules have been developed by adding these synthetic carbohydrates to macromolecules and to middle and low molecular weight molecules with different properties. These glycan-conjugated molecules have biological activities comparable to or higher than those of natural compounds, and present unique functions. In this review, several synthetic glycan-conjugated molecules are taken as examples to show design, synthesis and function.

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