Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: Synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity

Frydrych, Jan; Keough, Dianne T.; Chavchich, Marina; Travis, Jye; Dračínský, Martin; Edstein, Michael D.; Guddat, Luke W.; Hocková, Dana; Janeba, Zlatko

doi:10.1016/j.ejmech.2021.113416

Cited by 9 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Frydrych et al [ 83 ] used commercially available d - and l -prolinol as the starting material for the synthesis of novel antimalarial agents, yielding new chiral compounds in which a pyrrolidine ring is incorporated in the linker connecting the purine base to the phosphonate group(s) ( 119a,b and 120a,b ) (Fig. 24 ).…”

Section: Pyrrolidine Derivatives From Commercial Building Blocksmentioning

confidence: 99%

Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds

et al. 2021

View full text Add to dashboard Cite

The five-membered pyrrolidine ring is one of the nitrogen heterocycles used widely by medicinal chemists to obtain compounds for the treatment of human diseases. The great interest in this saturated scaffold is enhanced by (1) the possibility to efficiently explore the pharmacophore space due to sp3-hybridization, (2) the contribution to the stereochemistry of the molecule, (3) and the increased three-dimensional (3D) coverage due to the non-planarity of the ring—a phenomenon called “pseudorotation”. In this review, we report bioactive molecules with target selectivity characterized by the pyrrolidine ring and its derivatives, including pyrrolizines, pyrrolidine-2-one, pyrrolidine-2,5-diones and prolinol described in the literature from 2015 to date. After a comparison of the physicochemical parameters of pyrrolidine with the parent aromatic pyrrole and cyclopentane, we investigate the influence of steric factors on biological activity, also describing the structure–activity relationship (SAR) of the studied compounds. To aid the reader’s approach to reading the manuscript, we have planned the review on the basis of the synthetic strategies used: (1) ring construction from different cyclic or acyclic precursors, reporting the synthesis and the reaction conditions, or (2) functionalization of preformed pyrrolidine rings, e.g., proline derivatives. Since one of the most significant features of the pyrrolidine ring is the stereogenicity of carbons, we highlight how the different stereoisomers and the spatial orientation of substituents can lead to a different biological profile of drug candidates, due to the different binding mode to enantioselective proteins. We believe that this work can guide medicinal chemists to the best approach in the design of new pyrrolidine compounds with different biological profiles.

show abstract

Section: Pyrrolidine Derivatives From Commercial Building Blocksmentioning

confidence: 99%

Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Frydrych et al synthesized phosphoramidate prodrug containing purine nucleotide clubbed with pyrrolidine (80, Figure 21) with IC 50 of 7.2 μM (PfD6) and 2.5 μM (PfW2) having non-cytotoxicity against HepG2 and NHDF cell lines at 100 μM. [98] Uche et al studied three bisbenzylisoquinoline alkaloids including cycleanine, isochondodendrine, 2'-norcocsuline and two semisynthetic analogues of cycleanine (81 and 82). Compounds 81 and 82 were found with better activity than these alkaloids against PfDd2 strains (SYBR green 1 fluorescence assay) with IC 50 of 0.7 μM and 1.8 μM, respectively.. [99] Herein, IC 50 of other alkaloids were reported to be inferior against PfW2 and PfD6 strains as compared to PfDd2 strains.…”

Section: Othersmentioning

confidence: 99%

“…Seanego and co-workers have identified 7H-pyrrolo[2,3d]pyrimidine-4-amine (97) with IC 50 of 14.2 μM against Pf3D7 strains inhibiting calcium-dependent protein kinase (a target involved in maturation of gametocytes) PfCDPK1 (> 2 μM) and PfCDPK4 (0.53 μM) without any cytotoxicity against mammalian cell lines. [111] Bailey and his co-workers have identified triazolopyrimidine (98) with IC 50 of 0.06 μM through the high throughput screening of the Janssen Jumpstarter library. [112] The evaluation of the activity of 98 against PfDd2 and P. knowlesi revealed its EC 50 of 0.07 and 1.18, respectively.…”

Section: Othersmentioning

confidence: 99%

See 1 more Smart Citation

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Dhameliya,

Patel,

Kathuria

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Malaria remains a severe infectious disease caused by Plasmodium parasites among the primarily afflicting impoverished populations. According to World Health Organization (WHO) report, there were an estimated 247 million malarial cases globally, resulting in approximately 6,19,000 fatalities. Particularly prevalent in tropical and subtropical regions, the development of drug resistance has exacerbated this public health challenge. Consequently, there has been a concrete effort to explore novel compounds with anti‐malarial properties. In continuation of our previous works, this review focuses on heterocyclic compounds documented in 2021 and 2022, including artemisinin, benzimidazole, benzofuran, β‐lactam, coumarin, furan, indole, morpholine, piperazine, pyrimidine, quinoline, triazole, etc. highlighting their efficacy, structural characteristics, in vitro and in vivo activities, among other relevant aspects for the broad interest of medicinal chemists working on the design and development of novel anti‐malarial agents.

show abstract

“…75 The emergence of new Plasmodium drugresistant strains necessitates the development of new medicines with novel chemotypes and modes of action. Recently, Frydrych et al 76 employed commercially available D-and L-prolinol were used as the starting materials to synthesize nucleotide analogues with a pyrrolidine ring and incorporated with a linker connecting the purine base to a phosphonate group. All synthesized compounds were evaluated for their inhibitory activity against plasmodial hypoxanthine-guanine-(xanthine)-phosphoribosyltransferase from Plasmodium vivax (HGPRT), P. falciparum (HGXPRT), and human (HGPRT).…”

Section: Mementioning

confidence: 99%

Five-Membered Nitrogen Heterocycles as New Lead Compounds in Drug Discovery

Sazali Hamzah,

Fazli Mohammat,

Wibowo

et al. 2022

HETEROCYCLES

View full text Add to dashboard Cite

Five-membered nitrogen heterocyclic compounds are a very important group with various pharmaceutical properties. The different substitutions and functionalization of these compounds contributed to various biological activities.Five-membered nitrogen heterocyclic scaffolds are used for synthesizing numerous natural and synthetic compounds with a significant biological application. They include antidiabetic, anticancer, antimalarial, antiviral, antimicrobial, antiinflammatory, antibacterial, and anti-neurodegenerative agents. This mini-review provides an overview of the biological activities and the synthetic methods for preparing the five-membered nitrogen heterocyclic scaffolds and their functionalization. In the final part, this mini-review also listed some commercial drugs containing five-membered nitrogen heterocyclic motifs, highlighting the versatility of the five-membered nitrogen heterocyclic core in drug discovery. CONTENTS 1. Introduction 2. Biological activities and synthetic methodology of five-membered nitrogen heterocyclic compounds 2-1. Antidiabetic 2-2. Anticancer 2-3. Antibacterial 2-4. Antiviral244

show abstract

Nucleotide analogues containing a pyrrolidine, piperidine or piperazine ring: Synthesis and evaluation of inhibition of plasmodial and human 6-oxopurine phosphoribosyltransferases and in vitro antimalarial activity

Cited by 9 publications

References 33 publications

Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds

Pyrrolidine in Drug Discovery: A Versatile Scaffold for Novel Biologically Active Compounds

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

Five-Membered Nitrogen Heterocycles as New Lead Compounds in Drug Discovery

Contact Info

Product

Resources

About