Incorporating Selenium into Heterocycles and Natural Products─From Chemical Properties to Pharmacological Activities

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(6), P. 4436 - 4456

Published: March 4, 2022

Selenium (Se)-containing compounds have emerged as potential therapeutic agents for the treatment of a range diseases. Through tremendous effort, considerable knowledge has been acquired to understand complex chemical properties and biological activities selenium, especially after its incorporation into bioactive molecules. From this perspective, we compiled extensive literature evidence summarize critically discuss relationship between pharmacological selenium strategic organic molecules, heterocycles natural products. We also provide perspectives regarding challenges in selenium-based medicinal chemistry future research directions.

Language: Английский

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Small-molecule discovery through DNA-encoded libraries

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(9), P. 699 - 722

Published: June 16, 2023

Language: Английский

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Strategies for developing DNA-encoded libraries beyond binding assays

Nature Chemistry, Journal Year: 2022, Volume and Issue: 14(2), P. 129 - 140

Published: Feb. 1, 2022

Language: Английский

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DNA-encoded libraries (DELs): a review of on-DNA chemistries and their output

RSC Advances, Journal Year: 2021, Volume and Issue: 11(4), P. 2359 - 2376

Published: Jan. 1, 2021

A DNA-encoded library is a collection of small molecules covalently linked to DNA that has unique information about the identity and structure each member. chemical (DEL) broadly adopted by major pharmaceutical companies used in numerous drug discovery programs. The application DEL technology advantageous at initial period because reduced cost, time, storage space for identification target compounds. key points construction DELs comprise development selection encoding methods, transfer routine reaction from off-DNA on-DNA, exploration new reactions on DNA. limitations diversity were gradually using novel DNA-compatible based formation cleavage various bonds. Here, we summarized series chemistry building blocks analysed druggability screened hit via past five years.

Language: Английский

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gem ‐Difluoromethylene Alkyne‐Enabled Diverse C−H Functionalization and Application to the on‐DNA Synthesis of Difluorinated Isocoumarins

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(4), P. 1959 - 1966

Published: Oct. 6, 2020

Using gem-difluoromethylene alkynes as effectors, unprecedented diverse C-H activation/[4+2] annulations of simple benzoic acids are reported. The chemodivergent reaction outcomes well-tuned by Rh/Ir-catalyzed system; in the RhIII catalysis, 3-alkenyl-1H-isochromen-1-one and 3,4-dialkylideneisochroman-1-one skeletons afforded a solvent-dependent manner whereas difluoromethylene-substituted 1H-isochromen-1-ones generated under IrIII -catalyzed system. Mechanistic studies revealed that unusually double β-F eliminations fluorine effect-induced regioselective reductive elimination independently involved to enable distinct modes for divergent product formations. Besides, synthetic application both derivatization obtained diene products on-DNA synthesis DNA-tagged difluorinated isocoumarin have been demonstrated, which manifested great potential utility developed protocols.

Language: Английский

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Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 19, 2021

K. galanga is an aromatic medicinal herb. It locally to India and distributed in China, Myanmar, Indonesia, Malaysia, Thailand. a Traditional Chinese Herb Medicine (TCHM), which has been applied treat cold, dry cough, toothaches, rheumatism, hypertension so on. In addition, it used widely as spices since its highly aromas. The aim of this review compile update the current progresses ethnomedicinal uses, phytochemistry, pharmacology toxicology . All data on were based different classical literary works, multiple electronic databases including SciFinder, Web Science, PubMed, etc. results showed that ninety-seven compounds have identified from rhizome , terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids esters. Modern studies revealed extracts or secondary metabolites herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, anti-angiogenesis effects, closely related abundant uses. conclusion, although previous research works provided various information more in-depth are still necessary systemically evaluate pharmacological activities, toxicity quality control

Language: Английский

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Evolution of chemistry and selection technology for DNA-encoded library

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(2), P. 492 - 516

Published: Oct. 11, 2023

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and non-self-replicating phenotypes, generating a diverse world. In analogy with biological world, DEL world can evolve by using central dogma, wherein DNA replicates PCR reactions to amplify genetic codes, sequencing transcripts information, DNA-compatible synthesis translates into phenotypes. Importantly, is key expanding space. Besides, evolution-driven selection system pushes chemicals under selective pressure, i.e., desired strategies. this perspective, we summarized recent advances in synthetic toolbox panning strategies, which will shed light on drug discovery harnessing vitro evolution via DEL.

Language: Английский

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Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3362 - 3384

Published: April 10, 2024

Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies. Compared to traditional bioactivity-based screening methods, encoding display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments promising tools pharmaceutical hit due their high efficiency, throughput, resource minimization. This review systematically summarizes the development history, typology, prospective applications of displayed technologies, including phage display, ribosomal mRNA yeast cell one-bead one-compound, DNA-encoded, peptide nucleic acid-encoded, new peptide-encoded examples preclinical clinical translation. We discuss progress novel targeted therapeutic agents, covering spectrum small-molecule inhibitors nonpeptidic macrocycles linear, monocyclic, bicyclic peptides, in addition antibodies. also address pending challenges future prospects drug discovery, size libraries, advantages disadvantages technology, translational potential, market space. intended establish comprehensive high-throughput strategy researchers developers.

Language: Английский

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Inhibitors of Immune Checkpoints: Small Molecule- and Peptide-Based Approaches

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(1), P. 68 - 68

Published: Jan. 4, 2024

The revolutionary progress in cancer immunotherapy, particularly the advent of immune checkpoint inhibitors, marks a significant milestone fight against malignancies. However, majority clinically employed inhibitors are monoclonal antibodies (mAbs) with several limitations, such as poor oral bioavailability and immune-related adverse effects (irAEs). Another major limitation is restriction efficacy mAbs to subset patients, which triggered extensive research efforts identify alternative approaches targeting checkpoints aiming overcome restricted mAbs. This comprehensive review aims explore cutting-edge developments checkpoints, focusing on both small molecule- peptide-based approaches. By delving into drug discovery platforms, we provide insights diverse strategies optimize molecules peptides checkpoints. In addition, discuss recent advances nanomaterials carriers, providing basis for development platforms immunotherapy. Ongoing focused peptide-inspired agents paves way developing orally bioavailable next-generation immunotherapies.

Language: Английский

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Functionalization of DNA-Tagged Alkenes with Diazo Compounds via Photocatalysis

Organic Letters, Journal Year: 2022, Volume and Issue: 24(11), P. 2208 - 2213

Published: March 15, 2022

To explore potential chemical space using DNA-encoded library (DEL) technology, the development of various types robust DNA-compatible reactions is urgently needed. Diazo compounds, which serve as valuable building blocks and important synthons in synthetic chemistry, have been rarely applied DEL synthesis, probably because their modifications bases phosphate backbone DNA. Herein we report two cases with alkenes diazo providing corresponding hydroalkylation cyclopropanation products moderate to excellent yields. Notably, these transformations not only provide new access C(sp3)–C(sp3) bond formation DELs functional group tolerance but also represent practical ligation methods introduce functionalized molecules into

Language: Английский

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