Pharmacochemical Study of Multitarget Amino Acids’ Hybrids : Design, Synthesis, In vitro, and In silico Studies
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
Introduction: Neuro-inflammation is a complex phenomenon resulting in several disorders.ALOX-5, COX-2, pro-inflammatory enzymes, and amino acid neurotransmitters are tightlycorrelated to neuro-inflammatory pathologies. Developing drugs that interfere with these targetswill offer treatment for various diseases.
Objective: Herein, we extend our previous research by synthesizing a series of multitarget hybridsof cinnamic acids with amino acids recognized as neurotransmitters.
Methods: The synthesis was based on an in silico study of a library of cinnamic amide hybrids withglycine, γ- aminobutyric, and L - glutamic acids. Drug-likeness and ADMET properties were subjectedto in silico analysis. Cinnamic acids were derived from the corresponding aldehydes byKnoevenagel condensation. The synthesis of the amides followed a two-step reaction with 1-hydroxybenzotriazole monohydrate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloridein dry dichloromethane and the corresponding amino acid ester hydrochloride salt in thepresence of N,N,-diisopropyl-Nethylamine.
Results: The structure of the synthesized compounds was confirmed spectrophotometrically. Thenew compounds, such as lipoxygenase, cyclooxygenase-2, lipid peroxidation inhibitors, and antiinflammatories,were tested in vitro. The compounds exhibited LOX inhibition with IC50 values inthe low μM region).
Conclusion: Compounds 18a, 23b, and 11c are strong lipid peroxidation inhibitors (99%, 78%, and92%). Compound 28c inhibits SLOX-1 with IC50 =8.5 μM whereas 11a and 22a highly inhibitCOX-2 (IC50 6 and 5 μM Hybrids 14c and 17c inhibit both enzymes. Compound 29c showed thehighest anti-inflammatory activity (75%). The in silico ADMET properties of 14c and 11a supporttheir drug-likeness.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Medicinal chemistry (Shariqah (United Arab Emirates)) - (2024) vom: 09. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fotopoulos, Ioannis [VerfasserIn] |
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| Links: |
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| Themen: |
Alzheimer’s disease |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.2174/0115734064279653240125081042 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368378993 |
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| 100 | 1 | |a Fotopoulos, Ioannis |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacochemical Study of Multitarget Amino Acids’ Hybrids |b Design, Synthesis, In vitro, and In silico Studies |
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| 500 | |a Date Revised 21.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a Introduction: Neuro-inflammation is a complex phenomenon resulting in several disorders.ALOX-5, COX-2, pro-inflammatory enzymes, and amino acid neurotransmitters are tightlycorrelated to neuro-inflammatory pathologies. Developing drugs that interfere with these targetswill offer treatment for various diseases | ||
| 520 | |a Objective: Herein, we extend our previous research by synthesizing a series of multitarget hybridsof cinnamic acids with amino acids recognized as neurotransmitters | ||
| 520 | |a Methods: The synthesis was based on an in silico study of a library of cinnamic amide hybrids withglycine, γ- aminobutyric, and L - glutamic acids. Drug-likeness and ADMET properties were subjectedto in silico analysis. Cinnamic acids were derived from the corresponding aldehydes byKnoevenagel condensation. The synthesis of the amides followed a two-step reaction with 1-hydroxybenzotriazole monohydrate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloridein dry dichloromethane and the corresponding amino acid ester hydrochloride salt in thepresence of N,N,-diisopropyl-Nethylamine | ||
| 520 | |a Results: The structure of the synthesized compounds was confirmed spectrophotometrically. Thenew compounds, such as lipoxygenase, cyclooxygenase-2, lipid peroxidation inhibitors, and antiinflammatories,were tested in vitro. The compounds exhibited LOX inhibition with IC50 values inthe low μM region) | ||
| 520 | |a Conclusion: Compounds 18a, 23b, and 11c are strong lipid peroxidation inhibitors (99%, 78%, and92%). Compound 28c inhibits SLOX-1 with IC50 =8.5 μM whereas 11a and 22a highly inhibitCOX-2 (IC50 6 and 5 μM Hybrids 14c and 17c inhibit both enzymes. Compound 29c showed thehighest anti-inflammatory activity (75%). The in silico ADMET properties of 14c and 11a supporttheir drug-likeness | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a Multitarget | |
| 650 | 4 | |a amino acids | |
| 650 | 4 | |a cyclooxygenase inhibitors | |
| 650 | 4 | |a hybrids | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a lipoxygenase inhibitors | |
| 650 | 4 | |a neuro-inflammation. | |
| 700 | 1 | |a Pontiki, Eleni |e verfasserin |4 aut | |
| 700 | 1 | |a Hadjipavlou-Litina, Dimitra |e verfasserin |4 aut | |
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