Synthesis of (±)-Cassumunins A and B, New Curcuminoid Antioxidants Having Protective Activity of the Living Cell against Oxidative Damage

Masuda, Toshiya; Matsumura, Hiroyuki; Oyama, Yasuo; Takeda, Yoshio; Jitoe, Akiko; Kida, and Atsuko; Hidaka, Kayo

doi:10.1021/np970555g

Cited by 35 publications

(29 citation statements)

References 17 publications

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“…There are many compounds having the MW greater than 500, but still have medicinal importance and used as drug. Anti-oxidant property of cassumunins A and B is well reported in the literature (Nagano et al 1997;Masuda et al 1998). Total solvent accessible surface area (SASA in Å 2 ) was calculated using a probe with a 1.4 Å radius.…”

Section: Principal Descriptors and Admet Analysismentioning

confidence: 84%

“…Similarly, curcumin congeners such as piperine, caffeic The anti-oxidative effects of cassumunins A and B were compared with those of curcumin and it was found that cassumunins A and B are more anti-oxidant than curcumin (Nagano et al 1997). Cassumunins A and B have shown stronger protective activity than curcumin against oxidative cell death induced by hydrogen peroxide in a rat (Masuda et al 1998). Docking study also suggests that cassumunins A and B may be more potent inhibitors of b-A aggregation than curcumin.…”

Section: Structural Conservation Of B-amentioning

confidence: 99%

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Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Singh

Gupta

Kesharwani

et al. 2013

Netw Model Anal Health Inform Bioinforma

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Alzheimer's disease (AD) is caused by the accumulation of beta-amyloid (b-A) in the brain that forms amyloid plaque. b-A is an oligo-peptide consisting of 39-42 amino acid residues, produced by proteolytic cleavage of amyloid precursor protein by secretase enzymes. Evolutionary trace and protein family analysis of b-A indicates that C-terminal residues of b-A are highly conserved and hydrophobic in nature. Prevalence of hydrophobic residues at C-terminal of b-A promote aggregation, and also provide the stability to b-A plaque due to hydrophobic-hydrophobic interaction between residues of b-A. In this work, designing, evaluation and screening of potent inhibitors for b-A formation were studied. Curcumin and some of its herbal congeners were taken into consideration, to evaluate their anti-alzheimeric property against b-A as well as with b-A fibrils. Most of these herbal compounds were found potent inhibitors of b-A aggregation than known drugs for AD. The binding affinity of cassumunins A and B was compared with that of curcumin and it was found that cassumunins A and B may cause more potent inhibition of b-A than curcumin. Principal descriptors as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for these compounds were predicted, and were found satisfactory.

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Section: Principal Descriptors and Admet Analysismentioning

confidence: 84%

Section: Structural Conservation Of B-amentioning

confidence: 99%

Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Singh

Gupta

Kesharwani

et al. 2013

Netw Model Anal Health Inform Bioinforma

View full text Add to dashboard Cite

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“…37 As illustrated in Scheme 1, the conjugation of 1 or 2 with flutamide-related analogs, utilized 2-bromo-2-methyl propanoic acid, which was reacted with 4-substituted-3-trifluoromethylphenylamines ( 3a-e ) in the presence of EDCI and DMAP to give corresponding amides ( 4a-e ) in 30-65% yields. Reaction of these amides with 1 or 2 in the presence of anhydrous cesium carbonate (sodium iodide was used as the catalyst for making 5 and 10 ) gave the desired compounds 5 - 12 ( 2-10% yields) (Scheme 1), along with the recovered starting materials ( 1 or 2 ) (recovery rates: 39%-92%).…”

Section: Resultsmentioning

confidence: 99%

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

Shi

Wada

Ohkoshi

et al. 2012

Bioorganic & Medicinal Chemistry

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In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide- or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono- and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC50 values of 41.8 μM (for LNCaP) and 39.1 μM (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-antiandrogen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, antiandrogens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression.

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“…Excess 2,4-pentanedione or ethyl 4-acetyl-5-oxo-hexanoate was used to avoid aldol condensation occurring at both terminals of the starting material and to produce the monoaryl intermediate 16a or 17a . 10 The intermediates were subsequently condensed with an appropriate second benzaldehyde to give the target compounds 16 and 17 .…”

Section: Chemistrymentioning

confidence: 99%

“…Symmetric curcumin analogues, including 20 – 23 , 29 , 31 , and 33 – 37 with varied substituents on the phenyl rings, were then synthesized by the general synthetic pathway shown in Scheme 5. 2,4-Pentanedione or ethyl 4-acetyl-5-oxo-hexanoate was condensed with an appropriately substituted benzaldehyde in EtOAc at 70 °C using a slightly modified method of Pederson et al 12 Boric anhydride was used to form a boron complex with 2,4-pentanedione or ethyl 4-acetyl-5-oxo-hexanoate in order to prevent Knoevenagel condensation 10 (Scheme 5). …”

Section: Chemistrymentioning

confidence: 99%

Novel curcumin analogs to overcome EGFR–TKI lung adenocarcinoma drug resistance and reduce EGFR–TKI-induced GI adverse effects

Wada

Lee

Hung

et al. 2015

Bioorganic & Medicinal Chemistry

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Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression as well as phosphorylation in two gefitinib-resistant lung adenocarcinoma cell lines, CL1-5 (EGFRwt) and H1975 (EGFRL858R+T790M). Based on the identified structure-activity relationships, methoxy substitution at C-3', C-4', or both positions favored inhibitory activity (compounds 1, 2, 5, 8–15, 17, 36), while compounds with more polar substituents were generally less active in both cell lines. Compound 36 with a fluorine substituent at C-6' and its protonated counterpart 2 did not lose activity, suggesting halogen tolerance. In addition, a conjugated linker was essential for activity. Among all evaluated curcumin derivatives, compound 2 showed the best inhibitory effects on both wild-type and mutant EGFR by efficiently inducing gefitinib-insensitive EGFR degradation. Compound 23 also reduced gefitinib-induced gastrointestinal damage in the non-transformed intestinal epithelial cell line IEC-18.

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Synthesis of (±)-Cassumunins A and B, New Curcuminoid Antioxidants Having Protective Activity of the Living Cell against Oxidative Damage

Cited by 35 publications

References 17 publications

Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Comparative docking and ADMET study of some curcumin derivatives and herbal congeners targeting β-amyloid

Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens

Novel curcumin analogs to overcome EGFR–TKI lung adenocarcinoma drug resistance and reduce EGFR–TKI-induced GI adverse effects

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