Cinnamic Derivatives as Antitubercular Agents: Characterization by Quantitative Structure–Activity Relationship Studies

Teixeira, Cátia; Ventura, Cristina; Gomes, J.R.; Gomes, Paula; Martins, Filomena

doi:10.3390/molecules25030456

Cited by 10 publications

(5 citation statements)

References 44 publications

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“…Hence, it appears that several derivatives (7-24) from this chemical class can act in different biological systems (see Table 1). (Peperidou et al, 2017) Antimicrobial Mycobacterium smegmatis (Teixeira et al, 2020) Enzymatic inhibition Lipoxygenase (LOX) (Landberg et al, 2020) Enzymatic inhibition Acetylcholinesterase (AchE) Ghafary et al, 2020) Source: Authors (2021).…”

Section: Bioactivity Of Cinnamic Acid and Its Derivativesmentioning

confidence: 99%

“…CA is recognised as an intermediate in the synthesis of many active compounds in plant species and also exhibits potent inhibition of protease enzymes, such as lipoxygenase. Several studies have shown that other acids found in nature (caffeic (2), ferulic (3), and pcoumaric (5) acids) and the phenolic kinematic derivatives, including those containing amide groups, display properties that contribute to the reduction and/or inhibition of free radicals and reactive oxygen species (ROS), which lead to the minimisation of the incidence of numerous degenerative, infectious, cardiovascular diseases, among others (Teixeira et al, 2020).…”

Section: The Biosynthesis Of Cinnamic Acid and Its Derivatives In Plant Speciesmentioning

confidence: 99%

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Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

França¹,

Correia²,

Castro³

et al. 2021

RSD

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The article aims to analyze the progress of the evolution of cinnamic acid derivatives through a bibliographic review, describing the main synthetic routes in obtaining this class, as well as remarkable biological applications and application of the structure-activity relationship (SAR) as a strategy for design pharmacologically active molecules. The methodology used consists of reading and analyzing articles, whose approach is descriptive, with data being collected regarding the therapeutic potential of derivatives of cinnamic acid and its relationship with structural scaffolding, as well as the most widely used synthetic approaches. As a result, it was observed that cinnamic acid and its derivatives from natural sources can be synthesized in appreciable quantities with varied synthetic routes, as well as being candidates for therapeutic agents, since they have several therapeutic applications against diabetes, infectious and degenerative diseases, among others, in addition to presenting activity such as pest control, which has attracted the attention of academic and industrial researchers. These compounds are highly versatile since their activity is intrinsically associated with the mode of interaction between the structure and its molecular target. However, in nature they are obtained in small quantities, therefore, the development of new approaches of synthetic methodologies to obtain such compounds in substantial quantities and linked to medicinal chemistry can contribute to the development of very effective bioactive molecules in comparison with their precursors.

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Section: Bioactivity Of Cinnamic Acid and Its Derivativesmentioning

confidence: 99%

Section: The Biosynthesis Of Cinnamic Acid and Its Derivatives In Plant Speciesmentioning

confidence: 99%

Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

França¹,

Correia²,

Castro³

et al. 2021

RSD

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“…In the last 10 years, interest in CA and its derivatives (esters, amides, aldehydes and alcohols) [ 5 ] has increased because of its many pharmacological activities, such as antituberculosis [ 6 , 7 , 8 , 9 ], antiviral [ 10 ], anticancer [ 11 , 12 , 13 , 14 , 15 , 16 ], mammary (MCF-7) and prostate (PC-3) inhibition, neoplastic cell growth, apoptosis inducement [ 17 , 18 , 19 ], anticholesterolemic [ 20 , 21 , 22 , 23 ], cardioprotective [ 24 ], antioxidant [ 25 , 26 , 27 , 28 ], anti-inflammatory [ 2 , 29 , 30 , 31 , 32 ], hepatoprotective [ 33 , 34 , 35 ], antidiabetic [ 36 , 37 , 38 ], antimalarial [ 39 ], anxiolytic [ 40 ], central nervous system depressant [ 41 ], neuroprotective [ 42 , 43 , 44 , 45 , 46 ], larvicidal agent [ 47 , 48 , 49 , 50 , 51 ], anti-leishmania [ 52 ], cosmetic […”

Section: Introductionmentioning

confidence: 99%

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

et al. 2023

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The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 μM), followed by compound 4 (672.83 μM) and compound 3 (726.36 μM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 μM), followed by compound 9 (550.96 μM) and compound 6 (626.62 μM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.

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“…In consequence, cinnamic acid and its derivatives are promising starting point on the path from molecules to drugs due to their low toxicity and wide spectrum of anti-infective potential [ 19 , 20 ]. In the search for new pharmacologically active agents a number of cinnamic acid anilides were prepared and tested to specify their antifungal, antibacterial, and antimycobacterial activity profile [ 21 , 22 , 23 , 24 , 25 ]. Based on the antileishmanial activity of dihydroxycinnamic compounds, where the catechol-like moiety is frequently involved in a metal (Mn 2+ ) coordination bond by one of its hydroxyl groups, we proposed the introduction of halogen into the molecular structure of N -arylcinnamammides.…”

Section: Introductionmentioning

confidence: 99%

Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides

Bąk

Kos

Degotte

et al. 2023

IJMS

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A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an ‘averaged’ selection-driven interaction pattern was produced based in namely ‘pseudo–consensus’ 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds.

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Cinnamic Derivatives as Antitubercular Agents: Characterization by Quantitative Structure–Activity Relationship Studies

Cited by 10 publications

References 44 publications

Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

Synthesis, applications and Structure-Activity Relationship (SAR) of cinnamic acid derivatives: a review

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides

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