Synthesis and Evaluation of a Series of 3,4,5‐Trimethoxycinnamic Acid Derivatives as Potential Antinarcotic Agents

Jung, Jae‐Chul; Moon, Sohyeon; Min, Dongguk; Park, Woo Kyu; Jung, Mankil; Oh, Seikwan

doi:10.1111/cbdd.12087

Cited by 17 publications

(10 citation statements)

References 27 publications

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“…: 135–136 °C; MM: 252.10 g/mol; 1 H NMR (200 MHz, CDCl 3 ) δ H 7.59 (d, J = 16.0 Hz, 1H), 6.73 (s, 2H), 6.33 (d, J = 16.0 Hz, 1H), 3.87 (s, 9H), 3.79 (s, 3H). 13 C NMR (50 MHz, CDCl 3 ) δ C 167.5, 153.5, 144.9, 140.1, 129.9, 117.1, 105.2, 61.1, 56.2, 51.8, IR ν max (KBr, cm −1 ) 3003, 1697, 2943, 2837, 1632, 1040, 1005, 1582, 1506, 851 [ 51 , 52 ].…”

Section: Methodsmentioning

confidence: 99%

“…Yield 98.8%; white solid, MM: 266.12 g/mol, m.p. : 65–66 °C; 1 H NMR (200 MHz, CDCl 3 ) δ H 7.53 (d, J = 16.0 Hz, 1H), 6.68 (s, 2H), 6.28 (d, J = 16.0 Hz, 1H), 4.19 (q, J = 6.0 Hz, 2H), 3.81 (s, 9H), 1.27 (t, J = 6.0 Hz, 3H), 13 C NMR (50 MHz, CDCl 3 ) δ C 166.8, 153.3, 144.5, 139.9, 129.8, 117.4, 105.1, 60.8, 60.4, 56.0, 14.3, IR ν max (KBr, cm −1 ) 2999, 2974, 2945, 2837, 1701, 1634, 1038, 997, 1583, 1506, 872 [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

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Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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“…en, the product was successively washed with 5% (w/v) NaHCO 3 and water and dried with anhydrous Na 2 SO 4 . Finally, the solvent was evaporated to yield the pure compound [27][28][29].…”

Section: General Procedures For Preparation Of Compound 35mentioning

confidence: 99%

Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues

Nóbrega

Silva

Filho

et al. 2019

Journal of Chemistry

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Piplartine is an alkamide found in different Piper species and possesses several biological activities, including antiparasitic properties. Thus, the aim of the present study was to evaluate a series of 32 synthetic piplartine analogues against the Leishmania amazonensis promastigote forms and establish the structure-activity relationship and 3D-QSAR of these compounds. The antileishmanial effect of the compounds was determined using the MTT method. Most compounds were found to be active against L. amazonensis. Among 32 assayed derivatives, compound (E)-(−)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity (IC50 = 0.007 ± 0.008 μM, SI > 10), followed by benzyl 3,4,5-trimethoxybenzoate (IC50 = 0.025 ± 0.009 μM, SI > 3.205) and (E)-furfuryl 3-(3,4,5-trimethoxyphenyl)-acrylate (IC50 = 0.029 ± 0.007 μM, SI > 2.688). It was found that the rigid substituents contribute to increasing antiparasitic activity against L. amazonensis promastigotes. The presence of the unsaturated heterocyclic substituent in the phenylpropanoid chemical structure (furfuryl group) resulted in a bioactive derivative. Molecular simplification of benzyl 3,4,5-trimethoxybenzoate by omitting the spacer group contributed to the bioactivity of this compound. Furthermore, bornyl radical appears to be important for antileishmanial activity, since (E)-(−)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity. These results show that some derivatives studied would be useful as prototype molecules for the planning of new derivatives with profile of antileishmanial drugs.

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“…In 2013, a series of TMCA analoges were synthesized and examined the antinarcotic activity [61]. Ester derivatives were synthesized by acyl chlorination of TMCA, among which ester S36 ( Fig.…”

Section: Synthetic Tmca Esters As Cns Agentsmentioning

confidence: 99%

“…Ku et al [61] combined carbazole with cinnamoyl group and measured the vascular barrier protective effects of derivatives. Fig.…”

Section: Synthetic Tmca Esters As Anti-inflammatory Agentsmentioning

confidence: 99%

Research progress in the biological activities of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives

Zhao

Song

Xie

et al. 2019

European Journal of Medicinal Chemistry

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a b s t r a c t TMCA (3,4,5-trimethoxycinnamic acid) ester and amide are privileged structural scaffolds in drug discovery which are widely distributed in natural products and consequently produced diverse therapeutically relevant pharmacological functions. Owing to the potential of TMCA ester and amide analogues as therapeutic agents, researches on chemical syntheses and modifications have been carried out to druglike candidates with broad range of medicinal properties such as antitumor, antiviral, CNS (central nervous system) agents, antimicrobial, anti-inflammatory and hematologic agents for a long time. At the same time, SAR (structure-activity relationship) studies have draw greater attention among medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is an urgent need for the medicinal chemists to further exploit the precursor in developing chemical entities with promising bioactivity and druggability. This review concisely summarizes the synthesis and biological activity for TMCA ester and amide analogues. It also comprehensively reveals the relationship of significant biological activities along with SAR studies.

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Synthesis and Evaluation of a Series of 3,4,5‐Trimethoxycinnamic Acid Derivatives as Potential Antinarcotic Agents

Cited by 17 publications

References 27 publications

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues

Research progress in the biological activities of 3,4,5-trimethoxycinnamic acid (TMCA) derivatives

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