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Synthesis of New Opioid Analgesic Peptide Analogues to Enkephalin (Leucine- and Methionine-Enkephalin)

A small number of researches were done in the design and synthesis of enkephalin analogues that are able to resist degradation effect of proteolytic enzymes with good bioavailability and half-lives.Through studying structure activity relationships we tried to incorporate phthalyl group, tryptophan and lysine amino acids in different positions in the basic backbone structure of the naturally occurring opioid Leu5- and Met5- enkephalin, in the hope that such insertion of these amino acids could induce interesting addition in the biological activity of these analogues with enhancement of their bioavailability, in addition to decrease side effects as addiction liability.

These synthesized peptides are:

  • Analogue I: phthalyl-tyrosyl-glycel-tryptophan methyl ester.
  • Analogue II: Boc-tyrosyl-glycyl-phenylalanyl-lysine ethyl ester. HBr.

According to the designed structures, the analogues were synthesized following the conventional solution method and they were identified using the following techniques: melting point, optical rotation, thin layer chromatography (TLC), infrared spectroscopy (IR), elemental analysis (CHN) and amino acid analysis.

Key words: peptide, phthalyl, opoioid analgesics

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Publication Date
Sun Dec 30 2012
Journal Name
Al-kindy College Medical Journal
Analgesic Effect of Melatonin in Mice

Background: Melatonin is the main hormone secreted by the pineal gland. This indole compound (N-acetyl-5-methoxytryptamine) is derived from serotonin after two biochemical steps. Melatonin has been implicated in some pharmacological effects including sedative/hypnotic, anticonvulsant activity and others. The aim of this study was to investigate the antinociceptive effect of different doses of melatonin administered i.p. to mice, and then, to find the dose- response line of melatonin in mice as analgesic agent.
Methods: The dose response effect of melatonin (10, 50, and 100mg/kg) were assessed against control using tail flick test in mice as a model of nociceptive pain. In this model, all doses of melatonin were given intraperitoneally

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Publication Date
Wed Aug 02 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Synthesis of 3-C-Spiro Ring Nucleoside Analogues, of Possible Biological Activity

In this study, new derivatives of 3-C-spiro ring nucleoside analogues were synthesized. The structures of these derivatives were characterized by infrared spectroscopy,1HNMR (some of them) and elemental analysis. The nucleoside derivatives were tested for inhibition of E-coli and were all found to be active.

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Publication Date
Fri Jan 01 2021
Journal Name
Materials Today: Proceedings
Synthesis of gamma biguanides butyric acid analogues as HDAC inhibitors and studying their cytotoxic activity

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Publication Date
Sat Apr 01 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Synthesis of 3 - 3 - gem - di - C -Nitromethyl Nucleoside Analogues of Possible Biological Activity

Synthesis of new nucleoside analogues of the type : 3¢ , 3¢ - gem – di – C – nitromethly , expected to have useful application in the chemotherapeutic treatment of AIDS , cancer and microbial infections. The synthesis involved the condensation of the appropriate sugar derivative ( i.e . 3¢ , 3¢ –  gem – di – C – nitromethly – 1–  ribofuranose ) with nitrogen bases , such as , uracil and theophllin following a multi step scheme starting from diacetone golucose (1) (scheme 1) .The prepared compound were identified by spectroscopic methods ; ir , mass , 1H and 13C nmr.

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Publication Date
Sun Nov 08 2015
Journal Name
مجلة كلية التربية الاساسية القاجسية
Synthesis, Characterization, and Antibacterial Properties of mixed ligand Complexes of (L-Leucine and 8-hydroxyquinoline) with some metals Ions

Publication Date
Thu Aug 01 2013
Journal Name
Biochemistry
Mechanistic Insights from the Binding of Substrate and Carbocation Intermediate Analogues to Aristolochene Synthase

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Publication Date
Sun Sep 01 2013
Journal Name
Baghdad Science Journal
Synthesis and Evaluation of Antimicrobial activity of several new Maleimides to Benzothiazole moiety

In this work, a series of new maleimides linked to substituted benzothiazole moiety were synthesized. Synthesis of these new cyclic imides were performed via three steps, the first one involved preparation of a series of 2-aminobenzothiazole substituted with different substituents via reaction of different primary aromatic amines with ammonium thiocyanate and bromine in glacial acetic acid. The prepared 2- amino benzothiozoles were introduced in the second step in reaction with maleic anhydride producing a series of N-(substituted benzothiazole-2-yl) maleamic acids.The resulted maleamic acids were dehydrated in the third step via treatment with acetic anhydride and anhydrous sodium acetate to afford a series of the desirable N-(substitu

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Publication Date
Fri Mar 31 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Evaluation of Analgesic Activity of Newly Synthesized Phthalyl- tyrosyl-glycin Sodium

Alteration in the backbone structure of the endogenously released opioid peptides Leu5/Met5 enkephalins may result in compounds having comparable profile of pharmacological activity but with different physicochemical properties and side effects. Phthalyl amino acid and phthalyl esters are among the derivatives that have been synthesized and evaluated for their antibacterial and antifungal activities.This study was conducted to evaluate the possible analgesic activity of phthalyl-tyrosyl-glycin sodium that has been recently synthesized by our team.The study was carried out on 24 albino mice using hot plate method. The animals were allocated in to three groups; the first group received saline and represent a control g

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Publication Date
Sun Jun 11 2017
Journal Name
Ibn Al-haitham Journal For Pure And Applied Sciences
Glucagon-like Peptide-1 Levels and Related Parameters in Rheumatoid Arthritis Patients Prone to Atherosclerosis

  The study aimed to estimate  the role of glucagon-like peptide-1 (GLP-1)  and visfatin as a novel  pro inflammatory marker in Rheumatoid Arthritis (RA ) according to the activity scores of disease to assess the possibility of introducing glucagon-like peptide-1 and visfatin in the diagnosis and monitoring of RA patients and to found the correlation  of visfatin level with GLP-1 and AIP in patients prone to atherosclerosis ,fifty  healthy individuals as control group (G1) and fifty rheumatoid arthritis (RA) patients (G2) were enrolled in this study with middle age  ranged (30 – 40) years and BMI ≥24 kg/m2. ESR ,RF, lipid profile, CRP,insulin, visfatin and GLP-1were determined. Results in t

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Publication Date
Sun Sep 06 2015
Journal Name
Baghdad Science Journal
Methionine as a Spacer between Poly Acrylic acid and Ampicillin

In this work a novel drug delivery system through modification of poly acrylic acid with Methionine as a spacer between the poly acrylic acid which was converted to its acyl chloride and reacted with Methionine as spacer unit which has been reacted with Ampicillin drug. In vitro drug release study had been conducted successfully in basic medium in pH 7.4 and acidic medium in pH 1.1 at 37?. Due to many problems associated with drug release and, this modification could decrease the side effect of drug. The prepared prodrug polymer was characterized by spectra method [FTIR and 1H?NMR]. Physical properties and intrinsic viscosity of drug polymer were determined. The good results were obtained in the presence of spacer unit with compar

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