Facile synthesis of antimalarial 1,2-disubstituted 4-quinolones from 1,3-bisaryl-monothio-1,3-diketones

Vinayaka, A. C.; Sadashiva, M. P.; Wu, Xianzhu; Biryukov, Sergei S.; Stoute, José A.; Rangappa, Kanchugarakoppal S.; Gowda, D. Channe

doi:10.1039/c4ob01455c

Cited by 22 publications

(13 citation statements)

References 24 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of PD on P. falciparum growth was assessed by a SYBR Green assay (65). Aliquots of a 100 mM stock solution of PD were 1:2 serially diluted with DMSO, and aliquots of these solutions were further diluted with RPMI 1640 medium to obtain 62-4000 M solutions.…”

Section: Assessment Of the Effect Of Pd On P Falciparum Growthmentioning

confidence: 99%

Small molecule–based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes

Wu¹,

Dayanand²,

Thylur³

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Malaria infections cause several systemic and severe single- or multi-organ pathologies, killing hundreds of thousands of people annually. Considering the existing widespread resistance of malaria parasites to anti-parasitic drugs and their high propensity to develop drug resistance, alternative strategies are required to manage malaria infections. Because malaria is a host immune response-driven disease, one approach is based on gaining a detailed understanding of the molecular and cellular processes that modulate malaria-induced innate and adaptive immune responses. Here, using a mouse cerebral malaria model and small-molecule inhibitors, we demonstrate that inhibiting MEK1/2, the upstream kinases of ERK1/2 signaling, alters multifactorial components of the innate and adaptive immune responses, controls parasitemia, and blocks pathogenesis. Specifically, MEK1/2 inhibitor treatment up-regulated B1 cell expansion, IgM production, phagocytic receptor expression, and phagocytic activity, enhancing parasite clearance by macrophages and neutrophils. Further, the MEK1/2 inhibitor treatment down-regulated pathogenic pro-inflammatory and helper T cell 1 (Th1) responses and up-regulated beneficial anti-inflammatory cytokine responses and Th2 responses. These inhibitor effects resulted in reduced granzyme B expression by T cells, chemokine and intracellular cell adhesion molecule 1 (ICAM-1) expression in the brain, and chemokine receptor expression by both myeloid and T cells. These bimodal effects of the MEK1/2 inhibitor treatment on immune responses contributed to decreased parasite biomass, organ inflammation, and immune cell recruitment, preventing tissue damage and death. In summary, we have identified several previously unrecognized immune regulatory processes through which a MEK1/2 inhibitor approach controls malaria parasitemia and mitigates pathogenic effects on host organs.

show abstract

Section: Assessment Of the Effect Of Pd On P Falciparum Growthmentioning

confidence: 99%

Small molecule–based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes

Wu¹,

Dayanand²,

Thylur³

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…A novel protocol for the synthesis of 1,2‐disubstituted 4‐quinolones in moderate to excellent yields from 1,3‐bisaryl‐monothio‐1,3‐diketone 125 and arylamine substrates was reported by Vinayaka et al in 2014 (Scheme ) . This protocol involved two steps for providing the quinolone derivatives.…”

Section: Development In the Syntheses Of 4‐quinolonesmentioning

confidence: 99%

Synthesis and Functionalization of 4‐Quinolones – A Progressing Story

Ghosh

Das

2019

Eur J Org Chem

View full text Add to dashboard Cite

4‐Quinolone derivatives are serving as active components in diverse families of drugs such as antibacterial, antiviral, antimalarial, anticancer, antitumor and anti‐HIV agents. They have also attracted the significant attention in synthetic chemistry due to their prolific development, pharmacokinetic properties and good tolerability. Recent years have observed an upsurge in the modification of the 4‐quinolone scaffold. This review covers (2002 to 2019) the progress of the developments in the syntheses as well as functionalization of 4‐quinolones in different positions.

show abstract

“…The development of antibiotic quinolone begun in 1962 with the discovery of nalidixic acid which was used to treat urinary tract infections (Lesher et al, 1962). Many diversely substituted 4-quinolones have been extensively investigated as anti-tumour (Nakamura et al, 2005), anti-viral (Santos et al, 2009), anti-diabetic (Edmont et al, 2000), anti-trypanosomal (Wube et al, 2011) and anti-malarial agents (Vinayaka et al, 2014). As part of our studies in this area, the title compound was synthesized to study its crystal structure.…”

Section: Structure Descriptionmentioning

confidence: 99%

2-(2-Chlorobenzoyl)-1-(3,4-dimethoxyphenyl)-3-iodoquinolin-4(1H)-one

Shankar¹,

Chandra

Vinayaka

et al. 2017

IUCr Data

View full text Add to dashboard Cite

In the title compound C 24 H 17 ClINO 4 , the iodoquinolinyl moiety (r.m.s. deviation = 0.044 Å ) makes dihedral angles of 87.44 (10) and 88.64 (10) with the chloro-and methoxy-substituted benzene rings, respectively. The methoxy groups are present in synperiplanar and antiperiplanar conformations with respect to the benzene ring they are bound to, as indicated by the C-C-O-C torsion angle values of À16.2 (3) and 177.6 (2) , respectively. The crystal structure features relatively strong methoxybenzene-C-HÁ Á ÁO(quinolinyl) hydrogen bonds, leading to helical supramolecular chains along the a-axis direction. Additional C-HÁ Á ÁO interactions along with -stacking [intercentroid distance = 3.6070 (16) Å between quinolyl-NC 5 and C 6 rings] consolidate the three-dimensional molecular packing.

show abstract

Facile synthesis of antimalarial 1,2-disubstituted 4-quinolones from 1,3-bisaryl-monothio-1,3-diketones

Cited by 22 publications

References 24 publications

Small molecule–based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes

Small molecule–based inhibition of MEK1/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes

Synthesis and Functionalization of 4‐Quinolones – A Progressing Story

2-(2-Chlorobenzoyl)-1-(3,4-dimethoxyphenyl)-3-iodoquinolin-4(1H)-one

Contact Info

Product

Resources

About