Insights on the synthesis of asymmetric curcumin derivatives and their biological activities

Khor, Poh Yen; Aluwi, Mohd Fadhlizil Fasihi Mohd; Rullah, Kamal; Lam, Kok Wai

doi:10.1016/j.ejmech.2019.111704

Cited by 32 publications

(25 citation statements)

References 89 publications

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“…Curcumin, a naturally occurring phytochemical and principal component of Curcuma longa, has exhibited broad pharmacological properties including antioxidant, anti-inflammatory, anti-cancer and anti-viral effects (Kocaadam & Åžanlier 1080;Lal, Gupta, Thavaselvam & Agarwal 2016;Wiggers et al 2017;Khor, Aluwi, Rullah & Lam 2019). Curcumin and its derivatives, due to its rich conventional medicinal interest, has undergone comprehensive in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Patel¹,

Rajendran²,

Pakala³

et al. 2020

Preprint

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COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74 % identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.<br>

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Section: Introductionmentioning

confidence: 99%

Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Patel¹,

Rajendran²,

Pakala³

et al. 2020

Preprint

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“…However, multiple structural-pharmacokinetic challenges such as low solubility and poor bioavailability during oral administration greatly limit its clinical application. Albeit, several strategies have been developed to overcome these disadvantages, one of the most common is the synthesis of novel curcumin derivatives that have better therapeutic properties and bioavailability [111,112]. From the viewpoint of the organic chemistry, curcumin exists in solution as a tautomeric keto form in acidic and neutral solutions while enol form in the alkaline medium.…”

Section: Curcumin Derivativesmentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

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“…Turmeric, obtained from the dried rhizomes of Curcuma longa (Zingiberaceae), is a golden colored material, commonly used around the world for seasoning and food coloring. Since antiquity, turmeric has been widely used in the treatment of several diseases in traditional Chinese and Indian medicine (traditionally known as Ayurveda, e.g., for the treatment of inflammatory diseases) [1][2][3]. Curcumin ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl) hepta-1,6-diene-3,5-dione) also known as diferuloylmethane, is the main chemical component of turmeric (accounting for up to 70%), belonging to the class of diarylheptanoid Molbank 2021, 2021, M1276 2 of 12 metabolites.…”

Section: Introductionmentioning

confidence: 99%

2-Chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]styryl}pyrimidine: Synthesis, Spectroscopic and Computational Evaluation

Chaves

Sueth-Santiago

Pinto

et al. 2021

Molbank

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A novel curcumin analog namely 2-chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]-styryl}pyrimidine (compound 7) was synthesized by three-step reaction. The condensation reaction of protected vanillin with 2-chloro-4,6-dimethylpyrimidine (6) was the most efficient step, resulting in a total yield of 72%. The characterization of compound 7 was performed by 1H and 13C nuclear magnetic resonance (NMR), as well as high-resolution mass spectrometry. The experimental spectrometric data were compared with the theoretical spectra obtained by the density functional theory (DFT) method, showing a perfect match between them. UV-visible spectroscopy and steady-state fluorescence emission studies were performed for compound 7 in solvents of different polarities and the results were correlated with DFT calculations. Compound 7 showed a solvatochromism effect presenting higher molar extinction coefficient (log ε = 4.57) and fluorescence quantum yield (ϕ = 0.38) in toluene than in acetonitrile or methanol. The simulation of both frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) suggested that the experimental spectra profile in toluene was not interfered by a possible charge transfer. These results are an indication of a low probability of compound 7 in reacting with unsaturated phospholipids in future applications as a fluorescent dye in biological systems.

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Insights on the synthesis of asymmetric curcumin derivatives and their biological activities

Cited by 32 publications

References 89 publications

Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Synthesis of Biologically Active Molecules through Multicomponent Reactions

2-Chloro-4,6-bis{(E)-3-methoxy-4-[(4-methoxybenzyl)oxy]styryl}pyrimidine: Synthesis, Spectroscopic and Computational Evaluation

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