5-Hydroxy-6-Quinaldic Acid as a Novel Molecular Scaffold for HIV-1 Integrase Inhibitors

Polański, Jarosław; Niedbala, Halina; Musioł, Robert; Podeszwa, Barbara; Tabak, Dominik; Palka, Anna; Mencel, A.; Finster, Jacek; Mouscadet, Jean François; Bret, Marc Le

doi:10.2174/157018006776286934

Cited by 38 publications

(32 citation statements)

References 6 publications

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“…The increased OH acidity differentiates, for example, compound 3 from the quinoline type cycles. The increased OH acidity favors lower IC 50 values (compare compound 14a with 13c), also according to our previous results [20,21]. The amidation of 10 yields compounds having IC 50 values similar to that of scaffold 10.…”

Section: Resultssupporting

confidence: 83%

“…Table (1) reports inhibition data for scaffolds 7-10 and amides 11-15. Actually, compounds 9 and 10 appeared to inhibit IN better than compound 7, with the IC 50 amounting for 47 and 42 µM [20], respectively. Scaffolds 8 and 8a appeared to have IC 50 values higher than 100 µM.…”

Section: Resultsmentioning

confidence: 97%

“…Although the affinity of such fragments is too low to ensure drug effectiveness, they appear useful for further construction of leads. In the current publication we synthesized new compounds with improved HIV-1 IN inhibition based on novel quinoline scaffolds [20]. These scaffolds were linked by amide function to aryl moieties similar to the p-fluorophenylmethyl group of compound 3.…”

Section: Introductionmentioning

confidence: 99%

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Fragment Based Approach for the Investigation of HIV-1 Integrase Inhibition

Polański¹,

Niedbala²,

Musioł

et al. 2007

LDDD

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HIV-1 integrase (IN) inhibition of a novel series of quinoline derivatives was investigated. The compounds were designed on the basis of quinoline molecular scaffolds that attempt to mimic the basic naphtyridine motif of the L-870810 HIV-1 IN inhibitor. It appeared that the IN inhibition of the novel compounds was limited by the electroacceptor substitution within quinoline. Although the compounds studied here indicate structural similarity to L-870810, they are much less efficient than this compound. This can be explained by differences in conformations and apparent magnesium complexing ability in the naphtyridine and quinoline based amides.

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Fragment Based Approach for the Investigation of HIV-1 Integrase Inhibition

Polański¹,

Niedbala²,

Musioł

et al. 2007

LDDD

Self Cite

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“…In spite of numerous RT inhibitors (including the nucleotide RT inhibitors (NRTIs) and non-nucleotide RT inhibitors (NNRTIs) have been discovered and developed, like other anti-HIV-1 inhibitors, effectiveness of currently approved NRTIs and NNRTIs have been hampered because of their severe side effects and the aggravation of viral variants resistant to HIV-1 drug (Boone, 2006;De Clercq, 2002;Sluis-Cremer, Wainberg, Schinazi, 2015;Yu et al, 2011). To circumvent this challenge, there is an urgent require to develop new, efficacy, selective and safe HIV-1 inhibitors having significant potency against drugresistant RT viral strains and less toxicity still remains a high priority for medical research (Huang et al, 2007;Polanski et al, 2006;Safakish et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and in vitro anti-HIV-1 evaluation of some N-arylsulfonyl-3-formylindoles

Che

Tian

Liu

et al. 2018

Braz. J. Pharm. Sci.

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As our ongoing work on research of anti-HIV-1 inhibitors, fifteen N-arylsulfonyl-3-formylindoles (3ao) were designed and prepared through two step synthetic route. Firstly, 3-formylindoles (2a-c) were synthesized via the Vilsmeier-Haack reaction. Subsequently, treatment of 2a-c with the appropriate arylsulfonyl chlorides led to the corresponding target compounds in excellent yields. All analogues were also preliminary evaluated in vitro for their inhibitory activity against HIV-1 replication. Among of all the reported analogues, three compounds 3c, 3g and 3i displayed significant anti-HIV-1 activity, with EC 50 values of 9.57, 11.04 and 5.02 μM, and TI values of 31. 89, 13.79 and 81.69, respectively. N-mnitrophenylsulfonyl-3-formylindole (3c) and N-m-nitrophenylsulfonyl-6-methyl-3-formylindole (3i) especially exhibited the best promising anti-HIV-1 activity. In addition, it demonstrated that insertion of a methyl group at the C-6 position of the indolyl ring and a nitro group at the meta position of the arylsulfonyl ring, as in compound 3i, resulted in both low cytotoxicity (CC 50 = 410.41 μM) and good antiviral activity.

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“…7 A series of compounds derived from 8-hydroxyquinolines and styryl quinoline were recently synthesized as potential HIV-1 integrase inhibitors. 8,9 Similarly, isatin β-thiosemicarbazone derivatives were found to demonstrate a range of antiviral activities against Maloney leukemia virus, vaccinia virus [10][11][12][13] and inhibit HIV-1 replication.…”

Section: Introductionmentioning

confidence: 99%

Moisture compatible and recyclable indium (III) chloride catalyzed and microwave assisted efficient route to substituted 1H-quinolin-2-ones

Siddiqui¹,

Shamim²,

Singh³

et al. 2010

Arkivoc

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An efficient three component synthesis of highly functionalized 4-methyl-1H-quinolin-2-ones in one-pot from readily available coumarin, hydrazine and isatin catalyzed by a recyclable and moisture compatible InCl 3 under microwave irradiation has been developed. The synthesis involves a InCl 3 catalyzed dehydrative nucleophilic substitution on the lactone moiety of coumarin by the isatin hydrazone resulting in the formation of N-substituted lactams, 6-substituted-4-methyl-1-(2-oxo-1,2-dihydroindol-3-ylidenamino)-1H-quinolin-2-ones.The coumarin based transformation into substituted 1H-quinolin-2-ones proceeded smoothly with quantitative yields at ambient temperature.

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5-Hydroxy-6-Quinaldic Acid as a Novel Molecular Scaffold for HIV-1 Integrase Inhibitors

Cited by 38 publications

References 6 publications

Fragment Based Approach for the Investigation of HIV-1 Integrase Inhibition

Fragment Based Approach for the Investigation of HIV-1 Integrase Inhibition

Synthesis and in vitro anti-HIV-1 evaluation of some N-arylsulfonyl-3-formylindoles

Moisture compatible and recyclable indium (III) chloride catalyzed and microwave assisted efficient route to substituted 1H-quinolin-2-ones

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