Design, Synthesis, and Antitumor Activity Evaluation of Artemisinin Bivalent Ligands

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 409 - 409

Published: Jan. 15, 2024

Five artemisinin bivalent ligands molecules 4a–4e were designed, synthesized, and confirmed by 1H NMR, 13C low-resolution mass spectrometry, the bioactivities of target compounds investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, HCT-116. The results showed 4a, 4d, 4e exhibited significantly inhibitory activity compared with dihydroartemisinin; compound has good biological inhibiting BGC-823 an IC50 value 8.30 μmol/L. Then, correlations validated molecular docking through established multi-target model, which that could bind well antitumor protein MMP-9.

Language: Английский

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Diagnosis and management of malaria in the intensive care unit

Journal of Intensive Medicine, Journal Year: 2023, Volume and Issue: 4(1), P. 3 - 15

Published: Nov. 3, 2023

Malaria is responsible for approximately three-quarters of a million deaths in humans globally each year. Most the morbidity and mortality reported are from Sub-Saharan Africa Asia, where disease endemic. In non-endemic areas, malaria most common cause imported infection associated with significant despite recent advancements investments elimination programs. Severe often requires intensive care unit admission can be complicated by cerebral malaria, respiratory distress, acute kidney injury, bleeding complications, co-infection. Intensive management includes prompt diagnosis early initiation effective antimalarial therapy, recognition appropriate supportive care. However, lack diagnostic capacities due to limited advances equipment, personnel, infrastructure presents challenge malaria. This article reviews clinical classification, diagnosis, as relevant critical clinicians, highlighting role capacity, treatment options,

Language: Английский

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Nanotherapeutics against malaria: A decade of advancements in experimental models

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2024, Volume and Issue: 16(2)

Published: March 1, 2024

Abstract Malaria, caused by different species of protists the genus Plasmodium , remains among most common causes death due to parasitic diseases worldwide, mainly for children aged under 5. One main obstacles malaria eradication is speed with which pathogen evolves resistance drug schemes developed against it. For this reason, it urgent find innovative therapeutic strategies offering sufficient specificity parasite minimize evolution and side effects. In context, nanotechnology‐based approaches are now being explored their use as antimalarial delivery platforms wide range advantages tuneable properties that they offer. However, major challenges remain be addressed provide a cost‐efficient targeted strategy contributing eradication. The present work contains systematic review systems generated during last 10 years. This article categorized under: Therapeutic Approaches Drug Discovery > Nanomedicine Infectious Disease

Language: Английский

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The antimalarial activity of 1,2,4‐trioxolane/trioxane hybrids and dimers: A review

Archiv der Pharmazie, Journal Year: 2022, Volume and Issue: 355(7)

Published: April 6, 2022

Abstract Malaria, a mosquito‐borne parasitic infection caused by protozoan parasites belonging to the genus Plasmodium , is dangerous disease that contributes millions of hospital visits and hundreds thousands deaths across world, especially in Sub‐Saharan Africa. Antimalarial agents are vital for treating malaria controlling transmission, 1,2,4‐trioxolane/trioxane‐containing agents, artemisinin its derivatives, own antimalarial efficacy low toxicity with unique mechanisms action. Moreover, artemisinin‐based combination therapies were recommended World Health Organization as first‐line treatment uncomplicated have remained mainstay malaria, demonstrating 1,2,4‐trioxolane/trioxane derivatives useful prototypes control eradication malaria. However, already developed resistance almost all currently available creating an urgent need search novel pharmaceutical interventions The purpose this review article provide emphasis on current scenario (January 2012 January 2022) hybrids dimers potential activity structure–activity relationships also discussed facilitate further rational design more effective candidates.

Language: Английский

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Design, Synthesis, and Antitumor Activities of Isomers of Artemisinin Dimer Derivatives

Chemistry & Biodiversity, Journal Year: 2023, Volume and Issue: 20(7)

Published: May 31, 2023

In recent years, numerous studies have reported on the anti-tumor properties of artemisinin and its derivatives. However, relationship between their chirality activity remains unknown. this study, we synthesized a series dimer derivatives with three different chiral structures tested antiproliferative in MCF-7 HepG2 cells using CCK-8 assay. Interestingly, discovered that β, β α, conformations at C-10 exhibited stronger than those an α configuration cells. Notably, compound 4 showed 0.06 μM This study demonstrates conformation derivatives, these potential to be developed into anti-cancer drugs.

Language: Английский

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Lewis Acids and Heteropoly Acids in the Synthesis of Organic Peroxides

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(4), P. 472 - 472

Published: April 13, 2022

Organic peroxides are an important class of compounds for organic synthesis, pharmacological chemistry, materials science, and the polymer industry. Here, first time, we summarize main achievements in synthesis by action Lewis acids heteropoly acids. This review consists three parts: (1) metal-based peroxides; (2) promoted non-metal-based acids; (3) application peroxides. The information covered this will be useful specialists field reactions processes oxygen-containing compounds, catalysis, pharmaceuticals, engineering.

Language: Английский

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Medicinal Chemistry Approaches for the Discovery of Plasmodium Falciparum Dihydroorotate Dehydrogenase Inhibitors as Antimalarial Agents

Future Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(14), P. 1295 - 1321

Published: July 1, 2023

Malaria is a severe human disease and global health problem because of drug-resistant strains. Drugs reported to prevent the growth Plasmodium parasites target various phases parasites' life cycle. Antimalarial drugs can inhibit key enzymes that are responsible for cellular development parasites. falciparum dihydroorotate dehydrogenase one such enzyme necessary de novo pyrimidine biosynthesis. This review focuses on medicinal chemistry approaches used discovery identification selective P. inhibitors as antimalarial agents. comprehensive discusses recent advances in therapeutic activity distinct chemical classes compounds drugs.

Language: Английский

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Natural compounds efficacy in complicated diabetes: A new twist impacting ferroptosis

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115544 - 115544

Published: Oct. 9, 2023

Ferroptosis, as a way of cell death, participates in the body's normal physiological and pathological regulation. Recent studies have shown that ferroptosis may damage glucose-stimulated islets β Insulin secretion programmed death T2DM target organs are involved pathogenesis its complications. Targeting suppression with specific inhibitors provide new therapeutic opportunities for previously untreated organs. Current suggest natural bioactive compounds, which abundantly available drugs, foods, medicinal plants treatment organs, recently received significant attention their various biological activities minimal toxicity, many compounds appear to role regulation Therefore, this review summarized potential strategies treat complications, providing lead phytochemical molecular nuclei future drug research development intervene T2DM.

Language: Английский

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Recent advances on patents of Plasmodium falciparum dihydroorotate dehydrogenase ( Pf DHODH) inhibitors as antimalarial agents

Expert Opinion on Therapeutic Patents, Journal Year: 2023, Volume and Issue: 33(9), P. 579 - 596

Published: Sept. 2, 2023

ABSTRACTIntroduction Pyrimidine nucleotides are essential for the parasite's growth and replication. Parasites have only a de novo pathway biosynthesis of pyrimidine nucleotides. Dihydroorotate dehydrogenase (DHODH) enzyme is involved in rate-limiting step pathway. DHODH biochemical target discovery new antimalarial agents.Area covered This review discussed development patented PfDHODH inhibitors published between 2007 2023 along with their chemical structures activities.Expert opinion 4th Thus, inhibition using species-selective has drawn much attention treating malaria, because they inhibit parasite without affecting normal human functions. Looking at current scenario drug resistance most available drugs, there huge need targeted newer agents. Newer agents unique mechanisms action may be devoid toxicity, adverse effects ability parasites to quickly gain resistance, can those Many were past, dependency Plasmodium on provided approach novel agents.KEYWORDS: falciparum dihydroorotate (PfDHODH)PfDHODH inhibitorsde pathwayMalariaantimalarial agentsDisclaimerAs service authors researchers we providing this version an accepted manuscript (AM). Copyediting, typesetting, resulting proofs will undertaken before final publication Version Record (VoR). During production pre-press, errors discovered which could affect content, all legal disclaimers that apply journal relate these versions also. Article highlightsThis provides overview as druggable treatment malaria.Information regarding drugs role malaria life cycle also included review.This summarises pathway.The covers detailed description 2023.The activities inhibitors, general synthetic schemes, review.The useful eliminating toxic effects.Declaration interestsP Gehlot supported by grant from INSPIRE Department Science & Technology (DST INSPIRE/IF210107). The no other relevant affiliations or financial involvement any organization entity interest conflict subject matter materials apart disclosed.Reviewer disclosuresPeer reviewers relationships disclose.Author contribution statementV. K. Vyas designed conceptualized idea. P. gathered literature patent-related information. was written revised Gehlot. V. supervised, edited, finalised framework article. approved manuscript.AcknowledgmentsThe thankful Nirma University, Ahmedabad, India work, part Doctor Philosophy (PhD) research work Pinky Gehlot, submitted IndiaAdditional informationFundingThis paper funded DST INSPIRE-Department Technology, assistance under Project number INSPIRE/[IF210107].

Language: Английский

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Studies of Potency and Efficacy of an Optimized Artemisinin-Quinoline Hybrid against Multiple Stages of the Plasmodium Life Cycle

Pharmaceuticals, Journal Year: 2021, Volume and Issue: 14(11), P. 1129 - 1129

Published: Nov. 6, 2021

A recently developed artemisinin-quinoline hybrid, named 163A, has been shown to display potent activity against the asexual blood stage of Plasmodium, malaria parasite. In this study, we determined its in vitro cytotoxicity mammalian cells, potency suppress P. berghei hepatic infection and decrease viability falciparum gametocytes, addition determining whether drug exhibits efficacy a mice. This hybrid compound low level cells and, conversely, high selectivity. It is prevention development as well killing denoting potential blockage transmission. The presents inhibitory for beta-hematin crystal formation, which subsequent assays revealed that endoperoxide component undergoes bioactivation by reductive reaction with ferrous heme towards formation heme-drug adducts; parallel, 7-chloroquinoline binding affinity ferric hemin. Both structural components co-operate enhance inhibition beta-hematin, bitopic ligand property essential arresting growth parasites. We demonstrated vivo an erythrocytic schizonticide agent comparison chloroquine/artemisinin combination therapy. Collectively, findings suggest highly operative on detoxification suppression, provides compelling evidence explaining action stage. For sporozoite gametocyte stages, conserves typically observed drugs, possibly achieved due redox chemistry heme.

Language: Английский

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