Quantitative Structure–Cytotoxicity Relationship of Azulene Amide Derivatives

Imanari, Kana; Hashimoto, Masashi; Wakabayashi, Hidetsugu; Okudaira, Noriyuki; Bandow, Kenjiro; Nagai, Junko; Tomomura, Mineko; Tomomura, Akito; Uesawa, Yoshihiro; Sakagami, Hiroshi

doi:10.21873/anticanres.13497

Cited by 10 publications

(15 citation statements)

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“…Cell culture. Human normal oral cells [gingival fibroblast (HGF), periodontal ligament fibroblast (HPLF), pulp cell (HPC)] (19) at 12~20 population doubling level (PDL) and OSCC cell lines (Ca9-22, HSC-2, HSC-3, HSC-4) (Riken Cell Bank, Tsukuba, Japan) were cultured at 37˚C in DMEM supplemented with 10% heatinactivated FBS and antibiotics under humidified 5% CO 2 atmosphere, as described previously (14)(15)(16).…”

Section: Figure 1 Structure Of Azulene (A) Guaiazulene (B) Alkylammentioning

confidence: 99%

“…Control cells were treated with the same amounts of DMSO present in each diluent solution. Cells were incubated for 48 h and the relative viable cell number was then determined by the MTT method, as described previously (14)(15)(16). The CC 50 was determined from the dose-response curve of triplicate samples.…”

Section: Figure 1 Structure Of Azulene (A) Guaiazulene (B) Alkylammentioning

confidence: 99%

“…As far as we know, anticancer potential of guaiazulene derivatives against human oral malignant cells has not yet been reported. This urged us to initiate the investigation of 10 alkylaminoguaiazulenes ( Figure 1C) (14), 10 guaiazulene amides ( Figure 1D) (15) and 14 azulene amide derivatives without or with 7-isopropylgroup ( Figure 1E, F) (16). We have reported that the introduction of an isopropyl group in the seven-member ring and an amide group rather than alkylamino group in the five-member ring of guaiazulene increased the specific cytotoxicity against malignant cells over non-malignant cells (14)(15)(16) (Figure 1).…”

mentioning

confidence: 99%

“…This urged us to initiate the investigation of 10 alkylaminoguaiazulenes ( Figure 1C) (14), 10 guaiazulene amides ( Figure 1D) (15) and 14 azulene amide derivatives without or with 7-isopropylgroup ( Figure 1E, F) (16). We have reported that the introduction of an isopropyl group in the seven-member ring and an amide group rather than alkylamino group in the five-member ring of guaiazulene increased the specific cytotoxicity against malignant cells over non-malignant cells (14)(15)(16) (Figure 1). Furthermore, quantitative structure-activity relationship (QSAR) analyses demonstrated the tight correlation of their tumor-specificity with hydrophobicity and molecular shape (15,16).…”

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confidence: 99%

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Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

et al. 2020

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Aim: The aim of this study was to investigate the antitumor potential of guaiazulene-3-carboxylate derivatives against oral malignant cells. Materials and Methods: Twelve guaiazulene-3-carboxylate derivatives were synthesized by introduction of either with alkyl group [1-5], alkoxy group [6, 7], hydroxyl group [8, 9] or primary amine [10-12] at the end of sidechains. Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC 50) against 3 human oral mesenchymal cell lines to that against 4 human oral squamous cell carcinoma (OSCC) cell lines. Potencyselectivity expression (PSE) was calculated by dividing TS value by CC 50 value against OSCC cell lines. Cell cycle analysis was performed by cell sorter. Results: [6, 7] showed the highest TS and PSE values, and induced the accumulation of both subG 1 and G 2 /M cell populations in HSC-2 OSCC cells. Quantitative structure-activity relationship analysis demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the 3D shape, electric state and ionization potential. Conclusion: Alkoxyl guaiazulene-3carboxylates [6, 7] can be potential candidates of lead compound for developing novel anticancer drugs.

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Section: Figure 1 Structure Of Azulene (A) Guaiazulene (B) Alkylammentioning

confidence: 99%

Section: Figure 1 Structure Of Azulene (A) Guaiazulene (B) Alkylammentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

et al. 2020

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“…Some azulene derivatives have pharmacological activity, and azulene sulfonic acid derivatives are especially used as anti-inflammatory drugs [ 1 , 2 , 3 ]. In recent years, azulene derivatives have also been reported to exhibit anti-tumor activity [ 4 , 5 , 6 , 7 ].…”

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confidence: 99%

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010–2020)

Shoji

Okujima

Ito

2020

IJMS

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Azulene derivatives with heterocyclic moieties in the molecule have been synthesized for applications in materials science by taking advantage of their unique properties. These derivatives have been prepared by various methods, involving electrophilic substitution, condensation, cyclization, and transition metal-catalyzed cross-coupling reactions. Herein, we present the development of the synthetic methods, reactivities, and physical properties for the heterocycle-substituted and heterocycle-fused azulenes reported in the last decade.

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Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

Han

Ren

et al. 2023

Chemistry & Biodiversity

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Guaiazulene and related derivatives were famous for diverse biological activities. In an effort to discover new highly efficient candidate drugs derived from guaiazulene, four series of guaiazulene derivatives were designed, synthesized, and evaluated for antiproliferation, antiviral, anti-inflammatory and peroxisome proliferatorsactivated receptor γ (PPARγ) signalling pathway agonist activities. Among them, two guaiazulene condensation derivatives showed selective cytotoxic activities towards K562 cell with IC 50 values 5.21 μM and 5.14 μM, respectively, accompanied by slight effects on normal cell viability. For the first time, one guaiazulene derivative from series I exhibited potent antiviral activity towards influenza A virus with IC 50 of 17.5 μM. A guaiazulenebased chalcone showed higher anti-inflammatory activity than positive drug indomethacin with an inhibitory rate of 34.29 % in zebrafish model in vivo. One guaiazulene-based flavonoid could strongly agitate PPARγ pathway at 20 μM, indicating the potential of guaiazulene derivatives to reduce obesity development and ameliorate hepatic steatosis. Preliminary in silico ADME studies predicted the excellent drug-likeness properties of bioactive guaiazulene derivatives.

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Quantitative Structure–Cytotoxicity Relationship of Azulene Amide Derivatives

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Cited by 10 publications

References 20 publications

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010–2020)

Design, Synthesis, and Biological Activity of Guaiazulene Derivatives

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