Browsing by Author "Chung, Hery"

Now showing 1 - 6 of 6
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    2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β₃-Adrenergic Activity
    (2017) Apablaza H., Gastón E.; Montoya, Luisa; Morales Verdejo, César Aarón; Mellado, Marco; Cuellar Fritis, Mauricio Alcides; Lagos, Carlos F.; Soto Delgado, Jorge; Chung, Hery; Pessoa Mahana, Carlos David; Jaime Mella
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    Motifs in Natural Products as Useful Scaffolds to Obtain Novel Benzo[d]imidazole-Based Cannabinoid Type 2 (CB2) Receptor Agonists
    (2023) Cho, Analia Young Hwa; Chung, Hery; Romero-Parra, Javier; Kumar, Poulami; Allara, Marco; Ligresti, Alessia; Gallardo-Garrido, Carlos; Pessoa-Mahana, Hernan; Faundez, Mario; Pessoa-Mahana, Carlos David
    The endocannabinoid system (ECS) constitutes a broad-spectrum modulator of homeostasis in mammals, providing therapeutic opportunities for several pathologies. Its two main receptors, cannabinoid type 1 (CB1) and type 2 (CB2) receptors, mediate anti-inflammatory responses; however, their differing patterns of expression make the development of CB2-selective ligands therapeutically more attractive. The benzo[d]imidazole ring is considered to be a privileged scaffold in drug discovery and has demonstrated its versatility in the development of molecules with varied pharmacologic properties. On the other hand, the main psychoactive component of Cannabis sativa, delta-9-tetrahydrocannabinol (THC), can be structurally described as an aliphatic terpenoid motif fused to an aromatic polyphenolic (resorcinol) structure. Inspired by the structure of this phytocannabinoid, we combined different natural product motifs with a benzo[d]imidazole scaffold to obtain a new library of compounds targeting the CB2 receptor. Here, we synthesized 26 new compounds, out of which 15 presented CB2 binding and 3 showed potent agonist activity. SAR analysis indicated that the presence of bulky aliphatic or aromatic natural product motifs at position 2 of the benzo[d]imidazoles ring linked by an electronegative atom is essential for receptor recognition, while substituents with moderate bulkiness at position 1 of the heterocyclic core also participate in receptor recognition. Compounds 5, 6, and 16 were further characterized through in vitro cAMP functional assay, showing potent EC50 values between 20 and 3 nM, and compound 6 presented a significant difference between the EC50 of pharmacologic activity (3.36 nM) and IC50 of toxicity (30-38 & mu;M).
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    New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists
    (MDPI, 2021) Faundez Parraguez, Manuel; Alarcon Miranda, Carlos; Cho, Young Hwa; Pessoa Mahana, Hernan; Gallardo Garrido, Carlos; Chung, Hery; Faundez, Mario; Pessoa Mahana, David
    The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.
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    Synthesis and docking of novel 3-indolylpropyl derivatives as new polypharmacological agents displaying affinity for 5-HT1AR/SERT
    (2016) Pessoa Mahana, Hernán; Silva Matus, Paul; Pessoa Mahana, Carlos David; Chung, Hery; Iturriaga Vásquez, Patricio; Quiroz, Gabriel; Möller Acuña, Patricia; Zapata Torres, Gerald; Saitz Barría, Claudio Antonio; Araya Maturana, Ramiro; Reyes Parada, Miguel
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    Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer's disease
    (2020) Rodríguez Lavado, J.; Gallardo Garrido, C.; Mallea, M.; Bustos, V.; Osorio, R.; Hodar Salazar, M.; Chung, Hery; Araya Maturana, Ramiro; Lorca, M.; Pessoa Mahana, Carlos David; Mella Raipán, Jaime Alberto; Saitz Barría, Claudio Antonio; Jaque Olmedo, Pablo César; Reyes Parada, M.; Iturriaga Vásquez, P.; Pessoa Mahana, Hernán