Annual reports in medicinal chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
JACS Au, Journal Year: 2024, Volume and Issue: 4(3), P. 951 - 957
Published: Feb. 20, 2024
Malaria is one of the most widespread diseases worldwide. Besides a growing number people potentially threatened by malaria, consistent emergence resistance against established antimalarial pharmaceuticals leads to an urge toward new drugs. Hybridization two chemically diverse compounds into bioactive product successful concept improve properties hybrid drug relative parent and also overcome multidrug resistance. 1,2,3-Triazoles are significant pharmacophore system among nitrogen-containing heterocycles with various applications, such as antiviral, antimalarial, antibacterial, anticancer agents. Several marketed drugs possess these versatile moieties, which used in wide range medical indications. While synthesis containing 1,2,3-triazole unit was described using Cu- Ru-catalyzed azide–alkyne cycloaddition, alternative metal-free pathway has never been reported for hybrids. However, green method that allows toxic expensive metals be replaced organocatalyst. Herein, we present artemisinin–triazole hybrids via facile Ramachary-Bressy-Wang organocatalyzed azide-carbonyl [3 + 2] cycloaddition (organo-click) reaction. The prepared highly potent vitro chloroquine (CQ)-resistant multi-drug-resistant Plasmodium falciparum strains (IC50 (Dd2) down 2.1 nM; IC50 (K1) 1.8 nM) compared CQ = 165.3 302.8 nM). Moreover, more efficacious suppressing parasitemia extending animal survival berghei-infected mice (up 100% up 40 days time) than reference artemisinin, illustrating potential hybridization powerful drug-discovery approach.
Language: Английский
Citations
8
Antibiotics, Journal Year: 2024, Volume and Issue: 13(2), P. 142 - 142
Published: Feb. 1, 2024
The synthesis and antiplasmodial evaluation of new hybrids combining the pharmacophore structures artemisinin, ciprofloxacin or norfloxacin, 7-chloroquinoline are reported in this study. first step for all syntheses is obtainment key piperazine esters intermediates bearing drugs norfloxacin. Using these platforms, 18 final compounds were synthesized through a multistep procedure with overall yields ranging between 8 20%. All screened their activity against chloroquine-resistant Plasmodium falciparum FcB1 strain. Compounds 20, 21, 22, 28, an artesunate fragment ciprofloxacin, exhibited IC50 values range 3.5–5.4 nM excellent selectivity indices. Among moiety on two them, 23 24, afforded 1.5 1.9 nM, respectively. They also showed most potent evaluated CQ-resistant Dd2 strain falciparum, demonstrating that those incorporating potent. Finally, combination either norfloxacin moieties single molecular entity proved to substantially enhance when compared administration unconjugated counterparts artesunate/ciprofloxacin artesunate/norfloxacin.
Language: Английский
Citations
4
European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(25)
Published: May 10, 2024
Abstract The ruthenium‐catalyzed azide‐alkyne cycloaddition (RuAAC) gives access to 1,5‐disubstitued triazoles in a single atom‐economical step and offers advantages compared its copper‐catalyzed counterpart that both terminal internal alkynes can be employed. This review summarizes recent findings this field during the last eight years, covering mechanistic investigations, synthetic developments, as well applications medicinal chemistry, polymer synthesis physical organic chemistry.
Language: Английский
Citations
4
Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
This review highlights the use of functionalized organo-Li, -Mg and -Zn reagents for construction selective functionalization 5- 6-membered fused bicyclic heteroaromatics. Special attention is given to discussion advanced syntheses preparation highly heteroaromatic scaffolds, including quinolines, naphthyridines, indoles, benzofurans, benzothiophenes, benzoxazoles, benzothiazoles, benzopyrimidines, anthranils, thienothiophenes, purine coumarins, chromones, quinolones phthalazines their heterocyclic derivatives. The organometallic used desired functionalizations these scaffolds are generally prepared
Language: Английский
Citations
2
Antimicrobial Agents and Chemotherapy, Journal Year: 2024, Volume and Issue: 68(7)
Published: June 20, 2024
ABSTRACT In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed, and their activity profile was characterized against drug-sensitive drug-resistant Plasmodium falciparum parasites. Two hybrids found display parasite growth reduction, stage-specificity, speed activity, additivity in drug combinations, stability hepatic microsomes similar levels those displayed by dihydroartemisinin (DHA). Conversely, rate chemical homolysis peroxide bonds is slower than DHA. From a mechanistic perspective, heme plays central role peroxide, inhibiting detoxification disrupting redox homeostasis. The exhibiting slow more potent reducing viability ART-resistant parasites ring-stage survival assay fast homolysis. However, both showed limited ART-induced quiescent quiescent-stage assay. Our findings are consistent with previous results showing that peroxide-containing may retain proliferating our data suggest this property does not overcome peroxides killing non-proliferating state.
Language: Английский
Citations
1
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6724 - 6724
Published: June 18, 2024
A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction acetals containing 2-chloroacetamide moiety with phenols related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated the induction cell apoptosis inhibition process glycolysis. In particular, bis(heteroaryl)methane two 4-hydroxy-6-methyl-2H-pyran-2-one moieties combine excellent in vitro efficacy an IC50 1.7 µM HuTu-80 human duodenal adenocarcinoma models high selectivity index 73. Overall, this work highlights therapeutic potential dimeric from functionalized builds starting point for development new anticancer agents.
Language: Английский
Citations
1
International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 282, P. 136984 - 136984
Published: Oct. 28, 2024
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 28, 2024
ABSTRACT In response to the spread of artemisinin (ART) resistance, ART-based hybrid drugs were developed and their activity profile was characterized against drug-sensitive drug-resistant Plasmodium falciparum parasites. Two hybrids found display parasite growth reduction, stage-specificity, speed activity, additivity in drug combinations, stability hepatic microsomes similar levels those displayed by dihydroartemisinin (DHA). Conversely, rate chemical homolysis peroxide bonds is slower than DHA. From a mechanistic perspective, heme plays central role inhibiting detoxification disrupting redox homeostasis. The exhibiting slow more potent reducing viability ART-resistant parasites ring-stage survival assay fast homolysis. However, both showed some limited ART-induced quiescent quiescent-stage assay. Our findings are consistent with previous results showing that peroxide-containing may retain proliferating our data suggest this property does not overcome peroxides killing non-proliferating state. GRAPHICAL Hepatic cell-host-mediated metabolism responsible for short plasma half-lives antimalarial artemisinins (ARTs), illustrated here rapid degradation can facilitate parasites, as 1 .
Language: Английский
Citations
0
Synthetic Communications, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 20
Published: Sept. 26, 2024
Language: Английский
Citations
0
Annual reports in medicinal chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Jan. 1, 2024
Language: Английский
Citations
0