Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells

Kumar, Sarvesh; Singh, Brajendra K.; Arya, Pragya; Malhotra, Shashwat; Thimmulappa, Rajesh K.; Prasad, Ashok K.; Eycken, Erik V. Van der; Olsen, Carl Erik; DePass, Anthony L.; Biswal, Shyam; Parmar, Virinder S.; Ghosh, Balaram

doi:10.1016/j.ejmech.2011.09.008

Cited by 16 publications

(14 citation statements)

References 33 publications

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“…For this study, a series of 32 analogues of 1 (Scheme 1) were synthesized, preserving the (E)-3-(3,4,5-trimethoxyphenyl)-acryloyl moiety on cinnamic esters and amides and changing this moiety on benzoic esters by removing the ethylene group between carbons 2 and 3. Side-chain modi cations were also evaluated changing the radical R to methyl (5), ethyl (6), propyl (7), iPr (8), butyl (9), pentyl (10), decyl (11), 2-methoxyethyl (12), 4-methoxybenzyl (13), phenylethyl (14), 4-methylphenylethyl (15), carvacryl (16), CHPh 2 (17), furfuryl (18), eugenyl (19), (−)-bornyl (20) and piperonyl (21) on cinnamic esters, and butyl (22), N,N-diethyl (23), octyl (24), cyclohexyl (25) benzyl (26), pyrrolidyl (27), 4-methylbenzyl (28), 4-methoxybenzyl (29), 4-uorobenzyl (30), 4-chlorobenzyl (31), 4-bromobenzyl (32) 2,4-dimethoxybenzyl (33), and 3,4-dimethoxybenzyl (34) on amides. e benzoic esters synthetized were 2methoxyethyl-3,4,5-trimethoxybenzoate (35) and benzyl 3,4,5-trimethoxybenzoate (36) [8][9][10][11][12].…”

Section: Introductionmentioning

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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Section: Introductionmentioning

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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“…Previously, we have reported the structure-activity relationship studies of these analogs and discussed that position and number of methoxy group in the aromatic ring of the cinnamoyl moiety or replacement of oxygen with sulfur is critical for their biological activities [16]. It is important to note that ETMTC was 200 times better than its natural P. longum analog [16].…”

Section: Discussionmentioning

confidence: 97%

“…ETMTC was derived as described earlier [16] and was administered orally from days 21 to 32 twice a day in 20 μL volume per dose. As described earlier [9], mice were sensitized by three intraperitoneal injections of 50 μg OVA in 4 mg aluminum hydroxide or 4 mg aluminum hydroxide on days 0, 7, and 14.…”

Section: Grouping Sensitization Challenge and Treatment Of Micementioning

confidence: 99%

“…In our earlier study, we found that cinnamate derivatives of natural plant source, Piper longum, were effective in inhibiting TNF-α induced expression of cell adhesion molecules in human endothelial cells [15]. Further, we synthesized various novel analogs of cinnamates, thiocinnamates and thionocinnamates; and structure-activity relationship studies of these analogs revealed that ethyl 3′,4′,5′-trimethoxythionocinnamate (ETMTC) was most efficient in inhibiting TNF-α induced expression of cell adhesion molecules [16]. Indeed, ETMTC was 200 times more potent than its natural derivative [16], and this could be due to the presence of sulfur group in ETMTC (Fig.…”

Section: Introductionmentioning

confidence: 96%

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A novel cinnamate derivative attenuates asthma features and reduces bronchial epithelial injury in mouse model

Kumar

Mabalirajan

Rehman

et al. 2013

International Immunopharmacology

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“…Kumar et al [77] reported that ester S61 (Fig. 13) isolated from Piper longum inhibited ICAM-1 (intercellularcelladhesionmolecule-1), VCAM-1 and E-selectin by the induction of TNF-a.…”

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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Novel natural product-based cinnamates and their thio and thiono analogs as potent inhibitors of cell adhesion molecules on human endothelial cells

Cited by 16 publications

References 33 publications

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

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

A novel cinnamate derivative attenuates asthma features and reduces bronchial epithelial injury in mouse model

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

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