Cinnamamide: An insight into the pharmacological advances and structure–activity relationships

Gaikwad, Nikhil Baliram; Nanduri, Srinivas; Madhavi, Y.V.

doi:10.1016/j.ejmech.2019.07.064

Cited by 57 publications

(43 citation statements)

References 81 publications

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“…Cinnamic acids are one of such privileged multi-target structures that occur naturally in all plants [ 13 , 14 , 15 ]. Cinnamic acids as well as hydroxy- and phenyl-substituted derivatives of cinnamic acids have been widely investigated due to their significant and varied biological effects including anti-inflammatory, antioxidant, hepatoprotective, antidiabetic, antidepressant/anxiolytic, antifungal, antibacterial, antiviral, and anticancer effects [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

et al. 2020

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A series of nineteen novel ring-substituted N-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against Staphylococcus aureus as the reference strain, two clinical isolates of methicillin-resistant S. aureus (MRSA), and Mycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 µM) against MRSA isolates than the commonly used ampicillin (MIC 45.8 µM). The screening of the cell viability was performed using THP1-Blue™ NF-κB cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)- 3-phenylprop-2-enamide (IC50 6.5 µM), none of the discussed compounds showed any significant cytotoxic effect up to 20 μM. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pKa calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

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Section: Introductionmentioning

confidence: 99%

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

et al. 2020

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“…This group of compounds possesses several potentially active moieties-styryl, amide (peptide-like [16]) bond, and aryl [17][18][19][20][21][22]. Thus, cinnamides can be considered as a privilege structure or a scaffold (a part) of more complex molecules in medicinal chemistry [23,24] The series of N-arylcinnamide derivatives presented in this work was previously tested for their anti-microbial activity (compounds 1-15 and 17) [25,26], and three new derivatives 16 and 18 were prepared and characterized. Based on the concepts of polypharmacology, multifactorial diseases, and multitarget drugs [27], as well as the above-mentioned results, a group of eighteen N-arylcinnamanilides was chosen for the screening of their ability to moderate the inflammation-like reaction in vitro.…”

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confidence: 99%

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

et al. 2019

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A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)-3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C (2,5) or C (2,6) positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.Molecules 2019, 24, 4531 2 of 15 drugs are directly obtained from plants or fungi or are "nature-inspired" [11]. One such molecule is cinnamic acid (CA). It is a small organic molecule, which can be found in many kinds of plants in pure form or as a part of more complicated structures. CA and its natural and synthetic derivatives possess many interesting biological effects, such as antimicrobial [12,13], anticancer [14], anti-oxidant [13], and anti-inflammatory activities [15].N-Arylcinnamides represent a group of synthetic derivatives of CA. This group of compounds possesses several potentially active moieties-styryl, amide (peptide-like [16]) bond, and aryl [17][18][19][20][21][22]. Thus, cinnamides can be considered as a privilege structure or a scaffold (a part) of more complex molecules in medicinal chemistry [23,24] The series of N-arylcinnamide derivatives presented in this work was previously tested for their anti-microbial activity (compounds 1-15 and 17) [25,26], and three new derivatives 16 and 18 were prepared and characterized. Based on the concepts of polypharmacology, multifactorial diseases, and multitarget drugs [27], as well as the above-mentioned results, a group of eighteen N-arylcinnamanilides was chosen for the screening of their ability to moderate the inflammation-like reaction in vitro. Results and Discussion ChemistryThe investigated compounds (previously published compounds 1-15 and 17 [25] and two new compounds, 16 and 18) were prepared using a one-step microwave-assisted synthesis, see Scheme 1. Briefly, the carboxyl group of CA was activated with phosphorus trichloride, and then...

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“…For the compounds with halogen substitutes on the phenyl ring, the position, number of substituents and the type of halogen affected the biological activity of the compounds. Para-substituted chloro-compound 14 (IC 50 = 4.54 µg/mL) was more active when compared to ortho-substituted compound 15 (IC 50 = 9.91 µg/mL), suggesting that the presence of chlorine on the para position enhanced the antibacterial activity of the compound [25]. Compound 17 with a 4-fluoro phenyl ring substitution was the most active of all the compounds containing fluorine with IC 50 = 0.36 µg/mL indicating that fluoro substitution favored anti-tuberculosis activity of the synthesized compound.…”

Section: Compounds %Fungal Growth In 05 Mmol/l Of Inhibitormentioning

confidence: 99%

“…Outstandingly, compound 20 with a carboxylic acid at the para position exhibited potent anti-TB activity (IC 50 = 0.045 µg/mL) when compared to cinnamic acid. Thus, generally, the presence of an electron-withdrawing group on the para position of the phenyl ring favored significant anti-TB activity [25]. Compounds with electron-withdrawing groups exhibited improved activity (compound 23 with IC 50 = 0.56 µg/mL was more active than compound 16 with IC 50 = 2.35 µg/mL) while compounds with electron-donating substituents on the phenyl ring did not display a significant anti-TB activity [24].…”

Section: Compounds %Fungal Growth In 05 Mmol/l Of Inhibitormentioning

confidence: 99%

“…Atmaram Upare et al synthesized cinnamic acid derivatives (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) (Figure 4) in which the carboxyl group was replaced with bioisostere 1,2,4-oxadiazole followed by substituting the phenyl ring of the cinnamic acid resulting in a series of novel styryl oxadiazoles. The compounds were tested in vitro at day 8 for their anti-tubercular activity against H37Ra strain of Mycobacterium tuberculosis (Table 2).…”

Section: Lunatus Aniger P Ostreatusmentioning

confidence: 99%

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Cinnamic Acid Derivatives and Their Biological Efficacy

Ruwizhi

Aderibigbe

2020

IJMS

245

134

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The role played by cinnamic acid derivatives in treating cancer, bacterial infections, diabetes and neurological disorders, among many, has been reported. Cinnamic acid is obtained from cinnamon bark. Its structure is composed of a benzene ring, an alkene double bond and an acrylic acid functional group making it possible to modify the aforementioned functionalities with a variety of compounds resulting in bioactive agents with enhanced efficacy. The nature of the substituents incorporated into cinnamic acid has been found to play a huge role in either enhancing or decreasing the biological efficacy of the synthesized cinnamic acid derivatives. Some of the derivatives have been reported to be more effective when compared to the standard drugs used to treat chronic or infectious diseases in vitro, thus making them very promising therapeutic agents. Compound 20 displayed potent anti-TB activity, compound 27 exhibited significant antibacterial activity on S. aureus strain of bacteria and compounds with potent antimalarial activity are 35a, 35g, 35i, 36i, and 36b. Furthermore, compounds 43d, 44o, 55g–55p, 59e, 59g displayed potent anticancer activity and compounds 86f–h were active against both hAChE and hBuChE. This review will expound on the recent advances on cinnamic acid derivatives and their biological efficacy.

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Cinnamamide: An insight into the pharmacological advances and structure–activity relationships

Cited by 57 publications

References 81 publications

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

Cinnamic Acid Derivatives and Their Biological Efficacy

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