Synthesis and Crystal Structures of Methyl 3,4,5-Trimethoxybenzoate and 1,2-Dihydro-2,2,4-Trimethylquinoline Derivatives

Fotie, Jean; Olvera, Alan; Ayer, Suraj K.; Djieutedjeu, Honore; Poudeu, Pierre F. P.

doi:10.1007/s10870-014-0556-9

Cited by 4 publications

(7 citation statements)

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“…As such, compounds 1 and 2 are methyl 3,4,5-trimethoxybenzoate derivatives closely related to methyl gallate and were prepared through electrophilic bromination and nitration, respectively, as illustrated in Scheme 1 . 43…”

Section: Resultsmentioning

confidence: 99%

“…44 The same reaction conditions were implemented to prepare of 2,2,4-trimethyl-1,2-dihydroquinoline derivatives ( 5 and 6 ) by reacting the corresponding aniline derivative with acetone through a Skraup-Doebner-Von-Miller quinoline synthesis mechanism (Scheme 3). 43, 45 Under identical conditions but using cyclopentanone instead of acetone (Scheme 4), compound 7 was produced. 45 On the other hand, reacting a 2,2,4-trimethyl-1,2-dihydroquinoline with either cyclohexanone or cyclopentanone produced compounds 8 and 9 , respectively, as illustrated in Scheme 5.…”

Section: Resultsmentioning

confidence: 99%

“…Crystal data: C 11 H 12 Br 2 O 5 , M r = 384.03 g/mol, Crystal system monoclinic, Space group Cc , a = 17.287(4) Å , b = 8.9326(2) Å, c = 9.0071(2) Å, α = 90°, β = 105.90(3)°, γ = 90°, V = 1337.64(5) Å 3 , T = 100(2) K, Z = 4, D x = 1.91 g/cm 3 , µ = 6.070 mm -1 , F(000) = 752, λ = 0.71073 Å. Full-matrix least-squares refinement led to a final R = 0.028, wR = 0.069 and GOF = 1.049 (see supplemental data for the molecular representation at 50% probability level. 43…”

Section: Methodsmentioning

confidence: 99%

“…Crystal data: C 11 H 13 NO 7 , M r = 271.22 g/mol, Crystal system monoclinic, Space group C2/c , a = 20.520(4) Å , b = 9.7438(2 Å, c = 24.434(5) Å, 〈 = 90°, ® = 99.46(3)°, © = 90°, V = 4818.96(2) Å 3 , T = 100(2) K, Z = 14, D x = 1.31 g/cm 3 , µ = 0.111 mm -1 , F(000) = 1988, λ = 0.71073 Å. Full-matrix least-squares refinement led to a final R = 0.032, wR = 0.099 and GOF = 1.033. 43…”

Section: Methodsmentioning

confidence: 99%

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Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

Boateng

Roy

Agbo

et al. 2022

Preprint

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Melanoma and nonmelanoma skin cancer are the most lethal and commonest forms of skin cancers affecting one fifth of the US population. With the aim of identifying new lead compounds as starting point for attaining cost effective therapies, a small library of about 90 molecules was screened in vitro against A375, SKMEL28, A431, SCC12 skin cancer cell lines. About 35 of them, mainly dihydroquinolines, CC and CN linked biphenyls, and substituted methyl gallate or aniline derivatives, displayed low micromolar range activities, primarily against the A431 and SCC12 squamous carcinoma cell lines, with only a handful of these compounds displaying any activity against the A375 and SKMEL28 melanoma cell lines. Compounds 11 (A431: IC50 = 5.0 lower case Greek muM, SCC12: IC50 = 2.9 lower case Greek muM, SKMEL-28: IC50 = 4.9 lower case Greek muM, A375: IC50 = 6.7 lower case Greek muM) and 13 (A431: IC50 = 5.0 lower case Greek muM, SCC-12: IC50 = 3.3 lower case Greek muM, SKMEL-28: IC50 = 13.8 lower case Greek muM, A375: IC50 = 17.1 lower case Greek muM) were the most active across all these cell lines. Furthermore, many of the hit compounds showed little to no activity against mammalian nontumorigenic immortalized HaCaT cells, with a far better selectivity index than cisplatin (a well-known anticancer agent used as a positive control). Compounds 11 and 13 significantly and dose dependently induced apoptosis of SCC12 and SKMEL28 cells as evidenced by the downregulation of Bcl2 and upregulation of Bax protein expression levels, and by cleaved caspase 3, caspase 9 and PARP levels. Both agents also significantly reduced scratch wound healing, colony formation, and activated expression levels of major cancer molecular targets such as RSK/AKT/ERK1/2 and S6K1. To provide a better attribute profile for each of the hit molecules, in silico target(s) prediction, pharmacokinetic and ADMET studies are also reported, together with some preliminary structure activity relationship outlines. The SwissTargetPrediction web-based tool identified CDK8, CLK4, nuclear receptor ROR, tyrosine protein-kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, as likely targets for these hit compounds. Furthermore, the SwissADME web_tool predicted these compounds to exhibit high GI tract absorption, good skin permeation, and a viable biodegradability profile. To summarize, these data highlight the promising anticancer potential of these small molecules leads, warranting further investigation and/or optimization towards obtaining clinical candidates for combatting both melanoma and nonmelanoma skin cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

Boateng

Roy

Agbo

et al. 2022

Preprint

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“…A summary of the fundamental crystal and refinement data is provided in No formation of mono-nitro product -methyl and ethyl 2-nitro-3,4,5-trimethoxybenzoates was (6) observed. Formation of mono-nitro product (6) takes place at the nitration of compound 4 by nitric acid in the medium of acetic acid [20].…”

Section: Methodsmentioning

confidence: 99%

Targeted Intermediates of Eudesmic Acid: Synthesis and X-ray Investigations

M.I.¹,

Ya.²,

Zh.³

2017

IJTSRD

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It was carried out synthesis of esters and their dinitro derivatives of 3,4,5-trimethoxybenzoic (eudesmic) acid. Esterification of eudesmic acid carried out n absolute methanol or ethanol and corresponding methyl and ethyl 3,4,5-trimethoxybenzoates (have been synthesized in good yields. It was revealed that nitration of these esters gives only dinitro products. The structure of the synthesized compounds of the methyl and ethyl 2,6 trimethoxybenzoates (4, 5) was determined by X diffraction analysis (XRD). In the asymmetric part of the crystal structures of 4, 5 one and two molecules are observed, respectively. In crystalline structures a flat nitro groups and carboxylic groups do not participate in the conjugation with aromatic rings. I structure of 4, an intermolecular C8-H...O9 hydrogen bond is observed, these H bonds link the molecules along the [010] axis. In the crystal structure of intermolecular C9B-H...O4A and C10B hydrogen bonds form chains along the [011 formed chains are cross linked by the intermolecular C9B-H...O5A hydrogen bonds.

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Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing

Boateng,

Roy,

Agbo

et al. 2023

Chem Biol Drug Des

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Melanoma and nonmelanoma skin cancers are among the most prevalent and most lethal forms of skin cancers. To identify new lead compounds with potential anticancer properties for further optimization, in vitro assays combined with in‐silico target fishing and docking have been used to identify and further map out the antiproliferative and potential mode of action of molecules from a small library of compounds previously prepared in our laboratory. From screening these compounds in vitro against A375, SK‐MEL‐28, A431, and SCC‐12 skin cancer cell lines, 35 displayed antiproliferative activities at the micromolar level, with the majority being primarily potent against the A431 and SCC‐12 squamous carcinoma cell lines. The most active compounds 11 (A431: IC50 = 5.0 μM, SCC‐12: IC50 = 2.9 μM, SKMEL‐28: IC50 = 4.9 μM, A375: IC50 = 6.7 μM) and 13 (A431: IC50 = 5.0 μM, SCC‐12: IC50 = 3.3 μM, SKMEL‐28: IC50 = 13.8 μM, A375: IC50 = 17.1 μM), significantly and dose‐dependently induced apoptosis of SCC‐12 and SK‐MEL‐28 cells, as evidenced by the suppression of Bcl‐2 and upregulation of Bax, cleaved caspase‐3, caspase‐9, and PARP protein expression levels. Both agents significantly reduced scratch wound healing, colony formation, and expression levels of deregulated cancer molecular targets including RSK/Akt/ERK1/2 and S6K1. In silico target prediction and docking studies using the SwissTargetPrediction web‐based tool suggested that CDK8, CLK4, nuclear receptor ROR, tyrosine protein‐kinase Fyn/LCK, ROCK1/2, and PARP, all of which are dysregulated in skin cancers, might be prospective targets for the two most active compounds. Further validation of these targets by western blot analyses, revealed that ROCK/Fyn and its associated Hedgehog (Hh) pathways were downregulated or modulated by the two lead compounds. In aggregate, these results provide a strong framework for further validation of the observed activities and the development of a more comprehensive structure–activity relationship through the preparation and biological evaluation of analogs.

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Synthesis and Crystal Structures of Methyl 3,4,5-Trimethoxybenzoate and 1,2-Dihydro-2,2,4-Trimethylquinoline Derivatives

Cited by 4 publications

References 28 publications

Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

Targeted Intermediates of Eudesmic Acid: Synthesis and X-ray Investigations

Multifaceted approach toward mapping out the anticancer properties of small molecules via in vitro evaluation on melanoma and nonmelanoma skin cancer cells, and in silico target fishing

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