Asymmetric organocatalysis: an enabling technology for medicinal chemistry

Chemical Society Reviews, Год журнала: 2021, Номер 50(3), С. 1522 - 1586

Опубликована: Янв. 1, 2021

This review provides a comprehensive overview of the recent applications organocatalytic strategies in pharmaceutical synthesis, with focus on preparation antiviral, anticancer, neuroprotective, cardiovascular, antibacterial and antiparasitic agents.

Язык: Английский

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An overview of spirooxindole as a promising scaffold for novel drug discovery

Expert Opinion on Drug Discovery, Год журнала: 2020, Номер 15(5), С. 603 - 625

Опубликована: Фев. 28, 2020

Introduction: Spirooxindole, a unique and versatile scaffold, has been widely studied in some fields such as pharmaceutical chemistry synthetic chemistry. Especially the application of medicine, quite few compounds featuring spirooxindole motif have displayed excellent broad pharmacological activities. Many identified candidate molecules used clinical trials, showing promising prospects.Areas covered: This article offers an overview different applications developments spirooxindoles (including related natural products their derivatives) process drug innovation, including anticancer, antimicrobial, anti–inflammatory, analgesic, antioxidant, antimalarial, antiviral Furthermore, crucial structure-activity relationships, molecular mechanisms, pharmacokinetic properties, main methods spirooxindoles-based derivatives are also reviewed.Expert opinion: Recent progress biological activity profiles demonstrated significant position present-day discovery. we believe that multidirectional development novel drugs containing this core scaffold will continue to be research hotspot medicinal future.

Язык: Английский

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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 6, 2023

Abstract Undruggable proteins are a class of that often characterized by large, complex structures or functions difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also great opportunity for treatment human diseases and attracted substantial efforts in the field medicine. Therefore, this review, we focus on recent development discovery targeting “undruggable” their application clinic. To make review well organized, discuss strategies proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction targeted nucleic acid-based approach, immunotherapy others.

Язык: Английский

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Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold

Molecules, Год журнала: 2023, Номер 28(2), С. 618 - 618

Опубликована: Янв. 7, 2023

Spirooxindoles occupy an important place in heterocyclic chemistry. Many natural spirooxindole-containing compounds have been identified as bio-promising agents. Synthetic analogs also synthesized utilizing different pathways. The present article summarizes the recent development of both and synthetic prepared from isatin or its derivatives reported last five years. spirooxindoles are categorized based on their mentioned biological properties.

Язык: Английский

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Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Сен. 14, 2022

Abstract Regulated cell death (RCD) is a critical and active process that controlled by specific signal transduction pathways can be regulated genetic signals or drug interventions. Meanwhile, RCD closely related to the occurrence therapy of multiple human cancers. Generally, subroutines are key tumorigenesis, which contributed our better understanding cancer pathogenesis therapeutics. Indole alkaloids derived from natural sources well defined for their outstanding biological pharmacological properties, like vincristine, vinblastine, staurosporine, indirubin, 3,3′-diindolylmethane, currently used in clinic under clinical assessment. Moreover, such compounds play significant role discovering novel anticancer agents. Thus, here we systemically summarized recent advances indole as agents targeting different subroutines, including classical apoptosis autophagic signaling crucial other ferroptosis, mitotic catastrophe, necroptosis, anoikis, cancer. further discussed cross talk between mediated combined strategies (e.g., 3,10-dibromofascaplysin with olaparib) exhibit therapeutic potential against various cancers regulating subroutines. In short, information provided this review on regulation targets expected beneficial design molecules greater thereby facilitating development new therapy. Graphic abstract

Язык: Английский

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Design and Application of Chiral Bifunctional 4-Pyrrolidinopyridines: Powerful Catalysts for Asymmetric Cycloaddition of Allylic N-Ylide

ACS Catalysis, Год журнала: 2022, Номер 12(12), С. 7221 - 7232

Опубликована: Июнь 2, 2022

We designed bifunctional 4-pyrrolidinopyridines as powerful Lewis base catalysts. The catalyst structure features a 4-hydroxy-2-(hydroxydiphenylmethyl)pyrrolidine-1-formyl group at the pyridine's C3 site and chiral side arm C2 position of p-pyrrolidine ring. An operationally simple three-step synthetic route allows for efficient economical preparation. In comparison with other bases, exhibits excellent efficiency stereoselectivity in asymmetric (3 + 2) cycloaddition allylic N-ylide generated situ from pyrazolone-derived Morita–Baylis–Hillman carbonate, providing platform construction spiropyrazolone derivatives. reaction mechanism was thoroughly studied. Control experiments DFT calculations illustrated origin chemoselectivity stereocontrol model. H-bonding is crucial control enantioselectivity diastereoselectivity. also successfully applied reactions, such an acylative dynamic kinetic resolution to synthesize phthalidyl ester, including prodrug Talmetacin.

Язык: Английский

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Radical Acylalkylation of 1,3-Enynes To Access Allenic Ketones via N-Heterocyclic Carbene Organocatalysis

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(8), С. 5229 - 5241

Опубликована: Март 29, 2022

An N-heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This strategy suitable for a broad spectrum substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest radical reaction pathway this acylalkylation process.

Язык: Английский

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A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

Medicinal Research Reviews, Год журнала: 2024, Номер 44(5), С. 2194 - 2235

Опубликована: Апрель 9, 2024

Abstract Metal complexes based on N ‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies cytotoxic metal–NHC yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer are not fully understood, some potential targets and modes action been identified. However, a comprehensive review their biological is currently absent. general, apoptosis caused by metal–NHCs common tumor cells. They can cause series changes after entering cells, such mitochondrial membrane (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, caspase activation, ultimately leading apoptosis. Therefore, detailed understanding influence cancer cell crucial. this review, we provide summary advances that trigger apoptotic death via different apoptosis‐related or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER thioredoxin reductase (TrxR) inhibition, so forth. We also discuss challenges, limitations, future directions elucidate emerging application

Язык: Английский

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Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Сен. 4, 2024

Язык: Английский

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MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma

Analytical Cellular Pathology, Год журнала: 2022, Номер 2022, С. 1 - 14

Опубликована: Июль 30, 2022

Glioblastoma is one of the most common malignant tumors in brain, and these glioblastoma patients have very poor prognosis. Ferroptosis involved progression various tumors, including glioblastoma. This study aims to determine involvement microRNA (miR)-147a regulating ferroptosis vitro.Human cell lines were transfected with inhibitor, mimic matched negative controls miR-147a presence or absence ferroptotic inducers. To knock down endogenous solute carrier family 40 member 1 (SLC40A1), cells small interfering RNA against SLC40A1. In addition, without treatment also incubated temozolomide (TMZ) investigate whether overexpression could sensitize human TMZ chemotherapy vitro.We found that level was decreased tissues significantly suppressed growth vitro. expression elevated upon erastin RSL3 stimulation. Treatment induced cells, inhibitors block mimic-mediated tumor suppression Conversely, inhibitor prevented erastin- RSL3-induced increased viability Mechanistically, we determined directly bound 3'-untranslated region SLC40A1 inhibited SLC40A1-mediated iron export, thereby facilitating overload, lipid peroxidation, ferroptosis. Furthermore, mimic-treated exhibited higher sensitivity than those treated control for first time targets induce

Язык: Английский

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