Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates

Panda, Siva S.; Girgis, Adel S.; Thomas, Sean J.; Capito, Jason E.; George, Riham F.; Salman, Asmaa; El-Manawaty, May A.; Samir, Ahmed

doi:10.1016/j.ejmech.2020.112293

Cited by 39 publications

(38 citation statements)

References 64 publications

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“…As per previous research findings, some of the synthesized curcumin–amino acid conjugate prodrugs also exhibited comparable anti-inflammatory activities to 10 mg/kg indomethacin (dose equimolar to 10.3 mg/kg curcumin) when administered to rats with carrageenan-induced paw edema [ 28 ]. However, in the previous study, the intraperitoneal route of administration was used.…”

Section: Discussionsupporting

confidence: 72%

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

Phumsuay

Muangnoi

Wasana

et al. 2020

IJMS

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Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimulated RAW 264.7 macrophage cells. CurDG reduced the increased levels of NO, IL-6, and TNF- α, as well as iNOS and COX-2 expression in cells to a greater extent than those of curcumin, along with the potent inhibition of MAPK (ERK1/2, JNK, and p38) activity. The anti-inflammatory effects were assessed in vivo by employing a carrageenan-induced mouse paw edema model. Oral administration of CurDG demonstrated significant anti-inflammatory effects in a dose-dependent manner in mice. The effects were significantly higher compared to those of curcumin at the corresponding doses (p < 0.05). Moreover, 25 mg/kg curcumin did not exert a significant anti-inflammatory effect for the overall time course as indicated by the area under the curve data, while the equimolar dose of CurDG produced significant anti-inflammatory effects comparable with 50, 100, and 200 mg/kg curcumin (p < 0.05). Similarly, CurDG significantly reduced the proinflammatory cytokine expression in paw edema tissues compared to curcumin (p < 0.05). These results provide the first experimental evidence for CurDG as a promising anti-inflammatory agent.

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Section: Discussionsupporting

confidence: 72%

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

Phumsuay

Muangnoi

Wasana

et al. 2020

IJMS

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“…Therefore, several approaches and formulation strategies have been used to improve the oral bioavailability of curcumin, such as nanoformulation, adjuvants, and prodrugs [ 9 , 15 , 16 , 17 , 18 ]. The prodrug approach for improving physicochemical and pharmacokinetic properties of curcumin includes conjugating curcumin with polymers [ 19 ], sugars [ 20 ], amino acids [ 21 ], retinoic acid [ 22 ], fatty acids [ 23 ], and dicarboxylic acids, such as succinic acid [ 24 , 25 ] and diglutaric acid [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice

et al. 2020

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The drug treatment for neuropathic pain remains a challenge due to poor efficacy and patient satisfaction. Curcumin has been reported to alleviate neuropathic pain, but its clinical application is hindered by its low solubility and poor oral bioavailability. Curcumin diglutaric acid (CurDG) is a curcumin prodrug with improved water solubility and in vivo antinociceptive effects. In this study, we investigated the anti-inflammatory mechanisms underlying the analgesic effect of CurDG in the chronic constriction injury (CCI)-induced neuropathy mouse model. Repeated oral administration of CurDG at a low dose equivalent to 25 mg/kg/day produced a significant analgesic effect in this model, both anti-allodynic activity and anti-hyperalgesic activity appearing at day 3 and persisting until day 14 post-CCI surgery (p < 0.001) while having no significant effect on the motor performance. Moreover, the repeated administration of CurDG diminished the increased levels of the pro-inflammatory cytokines: TNF-α and IL-6 in the sciatic nerve and the spinal cord at the lowest tested dose (equimolar to 25 mg/kg curcumin). This study provided pre-clinical evidence to substantiate the potential of pursuing the development of CurDG as an analgesic agent for the treatment of neuropathic pain.

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“…The most effective agents synthesized with cholinesterase properties (8e, 8g and 8h) were subjected for acute toxicological bio-assay in mice utilizing the standard technique. 38 None of the tested agents reveal any mortality rates or toxicological symptoms (including animal body, legs, hair or tail) at the tested doses (50, 100 and 250 mg kg À1 mice body weight) supporting the safe utility of the tested agents at the mentioned doses.…”

Section: Biological Studiesmentioning

confidence: 78%

Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]

et al. 2020

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Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates

Cited by 39 publications

References 64 publications

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

Molecular Insight into the Anti-Inflammatory Effects of the Curcumin Ester Prodrug Curcumin Diglutaric Acid In Vitro and In Vivo

Curcumin Diglutaric Acid, a Prodrug of Curcumin Reduces Pain Hypersensitivity in Chronic Constriction Injury of Sciatic Nerve Induced-Neuropathy in Mice

Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2′-pyrrolidine-3′,3′′-pyrrolidines]

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