Synthesis and antifungal evaluation of pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones

Ryu, Chong Kul; Yoon, Joo Hee; Song, Ae Li; Im, Hyun Ah; Kim, Ji Young; Kim, Aram

doi:10.1016/j.bmcl.2011.10.092

Cited by 16 publications

(6 citation statements)

References 13 publications

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“…In light of these findings, the next goal of scientists has been to introduce new quinone-containing compounds by offering new opportunities for the development of selective agents in the treatment of cancer. Recent studies from our research group Yildirim et al, 2017) and that of Ferreira (Dias et al 2018), Ryu (Ryu, Song, Lee, Hong, Yoon, & Kim, 2010;Ryu, Yoon, Song, Im, Kim, & Kim, 2012), Tandon (Tandon, Maurya, Kumar, Rashid, & Panda, 2014;Tandon et al, 2010), and Valderrama (Valderrama, Ibacache, Rodriguez, Theoduloz, & Benites, 2011;Valderrama, Leiva, Rodriguez, Theoduloz, & Schmeda-Hirshmann, 2008) have shown that electrophilic character of 1,4-quinones can undergo with neutral and/or anionic nucleophiles in different conditions in versatile reactions, thus leading to various biologically active (hetero)cyclic quinone structures for their pharmacological properties. In this regard, as a result of the immense value of quinone compounds in organic and medicinal chemistry, 1,4-quinones have been studied for over a half-century as an important class of building blocks and still continue to attract considerable attention due to the broad range of synthetic and medicinal applications Johnson-Ajinwo et al, 2018;Pingaew et al, 2015;Ravichandiran, Kannan, Ramasubbu, Muthusubramanian, & Samuel, 2016;Ravichandiran, Subramaniyan, et al, 2019;Tandon & Kumar, 2013;Valderrama et al, 2016;Wellington, 2015).…”

Section: Introductionmentioning

confidence: 99%

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

et al. 2020

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Herein, we report the synthesis and cytotoxic effects of novel chlorinated plastoquinone analogs (ABQ1–17) against different leukemic cells. Compounds ABQ3, ABQ11, and ABQ12 demonstrated a pronounced antiproliferative effect against chronic myelogenous leukemia (CML) K562 cell line with IC50 values of 0.82 ± 0.07, 0.28 ± 0.03, and 0.98 ± 0.22 μM, respectively. Among them, ABQ11 showed approximately three times higher selectivity than imatinib on CML. ABQ11‐treated CML cells induced significant apoptosis at low concentration. Inhibitory effect of ABQ11 against eight different tyrosine kinases, including ABL1, was investigated. ABQ11 inhibited ABL1 with IC50 value of 13.12 ± 1.71 μM, indicating that the moderate inhibition of ABL1 kinase is just an in‐part mechanism of its outstanding cellular activity. Molecular docking of ABQ11 into ABL1 kinase ATP‐binding pocket revealed the formation of some key interactions. Furthermore, DNA cleavage assay showed that ABQ11 strongly disintegrated DNA at 1 μM concentration in the presence of iron (II) complex system, assuming that the major mechanism for the anticancer effects of ABQ11 is DNA cleavage. In silico ADMET prediction revealed that ABQ11 is a drug‐like small molecule with a favorable safety profile. Taken together, ABQ11 is a potential antiproliferative hit compound that exhibits unique cytotoxic activity distinct from imatinib.

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Section: Introductionmentioning

confidence: 99%

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

et al. 2020

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“…Antiviral potency was improved with the 4,6-dimethoxy-substituted indole 9 , which was one of the more potent of the simply substituted analogues prepared . However, this compound was subject to O -demethylation at both of the methoxy substituents when incubated in liver microsomes (LM), raising the specter of the formation of the chemically reactive indoloquinone 11 in vivo . A solution to this problem was found in the C-6 azaindole 10 (BMS-488043), which largely preserved the antiviral properties of 9 while introducing a mildly basic nitrogen atom to the heterocyclic nucleus that obviates quinone formation .…”

Section: Screening For Mechanistically Unique Hiv-1 Inhibitorsmentioning

confidence: 86%

Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir

Meanwell¹,

Krystal²,

et al. 2017

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Human immunodeficiency virus-1 (HIV-1) infection currently requires lifelong therapy with drugs that are used in combination to control viremia. The indole-3-glyoxamide 6 was discovered as an inhibitor of HIV-1 infectivity using a phenotypic screen and derivatives of this compound were found to interfere with the HIV-1 entry process by stabilizing a conformation of the virus gp120 protein not recognized by the host cell CD4 receptor. An extensive optimization program led to the identification of temsavir (31), which exhibited an improved antiviral and pharmacokinetic profile compared to 6 and was explored in phase 3 clinical trials as the phosphonooxymethyl derivative fostemsavir (35), a prodrug designed to address dissolution- and solubility-limited absorption issues. In this drug annotation, we summarize the structure-activity and structure-liability studies leading to the discovery of 31 and the clinical studies conducted with 35 that entailed the development of an extended release formulation suitable for phase 3 clinical trials.

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“…IDO1 depletes tryptophan, with deficiencies in this essential amino acid leading to suppression of immune response to tumours [ 50 ]. 12-Unsubstituted and carboxylate ester derivatives of 8a , including ethylester 8d , exhibit anti-fungal activities [ 51 ]. Carboxylates 8e – h display micromolar anti-bactericidal activity against the Erdman strain of Mycobacterium tuberculosis , with the molecular target being a membrane-bound, iron−thiol reductase (IspQ) [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis

Haji,

Faizi,

Koutentis

et al. 2023

Molecules

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This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-f]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[e]perimidines, phenoxazinones, benz[f]pyrido[1,2-a]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-b]naphthoquinones, hypothesised as prodrugs. Compounds with very strong correlations to known TrxR inhibitors had inverse correlations to the expression of both reductase enzymes, NQO1 and TrxR, including naphtho[2,3-b][1,4]oxazepane-6,11-diones, benzo[a]carbazole-1,4-diones, pyranonaphthoquinones (including kalafungin, nanaomycin A, and analogues of griseusin A), and discorhabdin C. Quinoline-5,8-dione scaffolds based on streptonigrin and lavendamycin can correlate to either reductase. Inhibitors of TrxR are not necessarily (imino)quinones, e.g., parthenolides, while oxidising moieties are essential for correlations to NQO1, as with the mitosenes. Herein, an overview of synthetic methods and biological activity of each family of heterocyclic imino(quinone) is provided.

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Synthesis and antifungal evaluation of pyrido[1,2-a]indole-1,4-diones and benzo[f]pyrido[1,2-a]indole-6,11-diones

Cited by 16 publications

References 13 publications

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

A novel series of chlorinated plastoquinone analogs: Design, synthesis, and evaluation of anticancer activity

Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir

Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis

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