Phenyl pyrrolo [1,2-a] quinolines- finding of a key by-product during quinolinium salt preparation

Sumanth, Gopavaram; Lakshmikanth, Kyatagani; Saini, Surbhi Mahender; Mundhe, Priyanka; Shivaprasad, Kondreddy; Chandrashekharappa, Sandeep

doi:10.1016/j.molstruc.2022.134350

Cited by 7 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mdpi.com/article/10.3390/ijms242417354/s1. References [55][56][57][58][59][60][61] are cited in the supplementary materials. Funding: This research was supported by the Russian Science Foundation grants 19-74-10021 (investigation of s17 effects on HIV-1 and its mechanism of action) and 22-14-00073 (development of Ku70-IN complex formation inhibitor).…”

Section: Supplementary Materialsmentioning

confidence: 99%

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair

Anisenko,

Galkin,

Mikhaylov

et al. 2023

IJMS

View full text Add to dashboard Cite

Integration of HIV-1 genomic cDNA results in the formation of single-strand breaks in cellular DNA, which must be repaired for efficient viral replication. Post-integration DNA repair mainly depends on the formation of the HIV-1 integrase complex with the Ku70 protein, which promotes DNA-PK assembly at sites of integration and its activation. Here, we have developed a first-class inhibitor of the integrase-Ku70 complex formation that inhibits HIV-1 replication in cell culture by acting at the stage of post-integration DNA repair. This inhibitor, named s17, does not affect the main cellular function of Ku70, namely its participation in the repair of double-strand DNA breaks through the non-homologous end-joining pathway. Using a molecular dynamics approach, we have constructed a model for the interaction of s17 with Ku70. According to this model, the interaction of two phenyl radicals of s17 with the L76 residue of Ku70 is important for this interaction. The requirement of two phenyl radicals in the structure of s17 for its inhibitory properties was confirmed using a set of s17 derivatives. We propose to stimulate compounds that inhibit post-integration repair by disrupting the integrase binding to Ku70 KuINins.

show abstract

Section: Supplementary Materialsmentioning

confidence: 99%

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair

Anisenko,

Galkin,

Mikhaylov

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Indolizine is a bridged nitrogen-containing bicyclic heterocyclic moiety (de Souza et al, 2016;Lakshmikanth et al, 2023;Sumanth et al, 2023). It is a 10π electron conjugated planar electronic structure, also known as a bioisostere of indole (Sandeep et al, 2013a(Sandeep et al, , 2014Shivaprasad et al, 2023;Sumanth et al, 2023;Venugopala et al, 2018). The structure is aromatic in nature and has planarity.…”

Section: Introductionmentioning

confidence: 99%

“…Heterocyclic compounds are of great interest in organic chemistry, having various applications in natural products and synthetic pharmaceuticals (Dorai et al., 2023; Ningegowda et al., 2020; Uppar et al., 2021; Uppar, Chandrashekharappa, et al., 2020; Uppar, Mudnakudu‐Nagaraju, et al., 2020; Venugopala et al., 2020). Indolizine is a bridged nitrogen‐containing bicyclic heterocyclic moiety (de Souza et al., 2016; Lakshmikanth et al., 2023; Sumanth et al., 2023). It is a 10 π electron conjugated planar electronic structure, also known as a bioisostere of indole (Sandeep et al., 2013a, 2014; Shivaprasad et al., 2023; Sumanth et al., 2023; Venugopala et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and anti‐inflammatory properties of novel ethyl 3‐benzoyl‐7‐(trifluoromethyl)indolizine‐1‐carboxylate derivatives: In silico and in vitro analysis

Singh,

Kushwaha,

Tandon

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

Series of 7‐(Trifluoromethyl) substituted indolizine 4a‐g was synthesized using the one‐pot method. Spectroscopic techniques such as IR, 1H‐NMR, 13C‐NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a‐g compounds were tested for their anti‐inflammatory activity. In this study, we identified novel indolizine derivative compounds 4a‐g selectively targeting COX‐2 enzyme, tumor necrosis factor‐α (TNF‐α) and, interleukin‐6 (IL‐6). The in silico docking studies of 4a‐g showed that these compounds have a higher affinity for COX‐2 enzyme, TNF‐ α, and IL‐6. In silico ADME profile analysis predicts that these compounds have good gastrointestinal tract and blood–brain barrier absorption. In vitro studies showed that compound 4d significantly reduces the level of COX‐2 enzymes as compared to indomethacin. Compounds 4e, 4f, and 4a were also found to significantly reduce the level of TNF‐α, while compounds 4f, 4g, and 4d, showed a reduction in the level of IL‐6 when compared to indomethacin. Compounds 4a, 4d, and 4f also reduces nitric oxide (NO) level, compared to indomethacin. Overall, the current study illustrates significant anti‐inflammatory activities of these novel 7‐(Trifluoromethyl) substituted indolizine derivatives.

show abstract

“…This study is a continuation of our research work in the design and preparation of the nitrogen‐containing heterocyclic compound ‘Indolizine’ as an anti‐TB agent. Indolizines are prime focussed due to their interest in synthetic chemistry (Lakshmikanth et al., 2023; Sandeep et al., 2013a, 2014; Sumanth et al., 2023; Venugopala et al., 2018) with medicinal applications like tuberculosis (Khedr et al., 2018; Sandeep Chandrashekharappa et al., 2019; Venugopala, Chandrashekharappa, Pillay, et al., 2019; Venugopala, Tratrat, Chandrashekharappa, et al., 2019; Venugopala, Tratrat, Pillay, et al., 2019), antioxidant (Vijayakumar Uppar, 2020), anticancer (Sandeep, Padmashali, et al., 2016), anti‐microbial (Sandeep et al., 2013b; Uppar et al., 2021; Vijayakumar Uppar, 2020), anti‐inflammatory (Chandrashekharappa, Venugopala, Tratrat, et al., 2018; Sandeep et al., 2017; Venugopala, Al‐Attraqchi, Tratrat, et al., 2019; Venugopala, Chandrashekharappa, Tratrat, et al., 2021), larvicidal (Chandrashekharappa, Venugopala, Nayak, et al., 2018; Sandeep, Venugopala, et al., 2016; Uppar et al., 2020) and NmeNANAS inhibitor (Alwassil et al., 2019). In this work, we have designed, characterized and evaluated a series of morpholine‐containing indolizine derivatives (5a‐o) (Table 1) for their anti‐tubercular potential.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and characterization of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate as anti‐tubercular agents: In silico screening for possible target identification

Tiwari,

Mangubhai,

Kidwai

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

A thorough search for the development of innovative drugs to treat tuberculosis, especially considering the urgent need to address developing drug resistance, we report here a synthetic series of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues (5a‐o) as potent anti‐tubercular agents. These morpholino‐indolizines were synthesized by reacting 4‐morpholino pyridinium salts, with various electron‐deficient acetylenes to afford the ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate analogues (5a‐o). All synthesized intermediate and final compounds are characterized by spectroscopic methods such as 1H NMR, 13C NMR and HRMS and further examined for their anti‐tubercular activity against the M. tuberculosis H37Rv strain (ATCC 27294—American type cell culture). All the compounds screened for anti‐tubercular activity in the range of 6.25–50 μM against the H37Rv strain of Mycobacterium tuberculosis. Compound 5g showed prominent activity with MIC99 2.55 μg/mL whereas compounds 5d and 5j showed activity with MIC99 18.91 μg/mL and 25.07 μg/mL, respectively. In silico analysis of these compounds revealed drug‐likeness. Additionally, the molecular target identification for Malate synthase (PDB 5CBB) is attained by computational approach. The compound 5g with a MIC99 value of 2.55 μg/mL against M. tuberculosis H37Rv emerged as the most promising anti‐TB drug and in silico investigations suggest Malate synthase (5CBB) might be the compound's possible target.

show abstract

Phenyl pyrrolo [1,2-a] quinolines- finding of a key by-product during quinolinium salt preparation

Cited by 7 publications

References 27 publications

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair

Synthesis, characterization, and anti‐inflammatory properties of novel ethyl 3‐benzoyl‐7‐(trifluoromethyl)indolizine‐1‐carboxylate derivatives: In silico and in vitro analysis

Design, synthesis and characterization of ethyl 3‐benzoyl‐7‐morpholinoindolizine‐1‐carboxylate as anti‐tubercular agents: In silico screening for possible target identification

Contact Info

Product

Resources

About