Synthesis and anti-inflammatory activity evaluation of novel chroman derivatives

Matta, Akanksha; Sharma, Abhay; Tomar, Shilpi; Cao, Ping; Kumar, Sandeep; Balwani, Sakshi; Ghosh, Balaram; Prasad, Ashok K.; Eycken, Erik V. Van der; DePass, Anthony L.; Wengel, Jesper; Parmar, Virinder S.; Len, Christophe; Singh, Brajendra K.

doi:10.1039/d0nj02125c

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…On the other hand, chromone derivatives possess many different biological activities such as anticancer [ 31 , 32 , 33 ], antimicrobial [ 34 ], anti-inflammatory [ 35 , 36 ], antitubercular [ 37 , 38 ] and others activities [ 39 , 40 , 41 ], which have generated an interest in developing further this scaffold. The chromone scaffold is also present in some approved drugs such as flavoxate ( Figure 2 ), a muscarinic antagonist and spasmolytic.…”

Section: Introductionmentioning

confidence: 99%

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

et al. 2022

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Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.

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Section: Introductionmentioning

confidence: 99%

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

et al. 2022

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“…. The above data suggested that 1 would be a chroman derivative, which was similar to N-butyl-2,2-dimethylchroman-6-carboxamide, [20] except for the presence of a Δ 3,4 double bond and the replacement of the ethyl group at C-16 in N-butyl-2,2-dimethylchroman-6-carboxamide by a carboxylic group in 2. 1 2).…”

Section: Introductionmentioning

confidence: 76%

“…The 1 H NMR and 13 C NMR spectroscopic data (Table 2) revealed the presence of two methyls [δ H 1.41 (s, H 3 -11 and H 3 -12); δ C 28.3 (C-11 and C-12)], two methenes [δ H 3.59～3.64 (m, H 2 -15), 2.64 (t, J＝6.8 Hz, H 2 -16); δ C 36.5 (C-15, 34.5, C-16)], two olefinic methines [δ H 5.78 (d, J＝9.6 Hz, H-3), 6.42 (d, J＝9.6 Hz, H-4); δ C 132.2 (C-3, 122.5, C-4)], one oxygenated quaternary carbon [δ C 77.7 (C-2)], two carbonyls [δ C 167.2 (C-13), 173.6, (C-17)], an amino group [δ H 7.72 (br s, 14-NH)], and a trisubtituted benzene ring [δ H 7.59 (br s, H-5), 7.67 (br d, J＝8.4 Hz, H-7), 6.75 (d, J＝8.4 Hz, H-8); δ C 126.5 (C-5), 128.1 (C-6), 129.2 (C-7), 116.6 (C-8), 156.4 (C-9), 121.6 (C-10)]. The above data suggested that 1 would be a chroman derivative, which was similar to N-butyl-2,2-dimethylchroman-6-carboxamide,[20] except for the presence of a Δ 3,4 double bond and the replacement of the ethyl group at C-16 in N-butyl-2,2-dimethylchroman-6-carboxamide by a carboxylic group in 2 1. H-1 H COSY correlation between H-3 and H-4, and HMBC correlations between H-4/ C-2, H-4/C-5, H-4/C-9, H-4/C-10, H-3/C-10, H 3 -12/C-2, and H 3 -12/C-3 demonstrated the existence of a Δ 3,4 double bond (Figure 2).…”

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confidence: 78%

Study on Secondary Metabolites of Marine-Derived Fungus Eutypella sp. F0219

Yi¹,

Shi²,

Binglin³

et al. 2023

Chinese Journal of Organic Chemistry

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研究论文海洋来源真菌 Eutypella sp. F0219 次级代谢产物研究易继凌 a,b 施康琦 a,b 吴冰林 a,b 黎婉珊 * ,a,b 陈光英 * ,a,b ( a 海南师范大学化学与化工学院热带药用资源化学教育部重点实验室海口 571158) ( b 海南师范大学化学与化工学院热带药用植物化学海南省重点实验室海口 571158) 摘要弯孢聚壳属真菌能产生结构丰富多样的活性化合物. 对一株来自海洋沉积物的真菌 Eutypella sp. F0219 代谢产物研究中, 分离得到一个新的异戊烯基取代二氢异香豆素和一个新的色烯酰胺衍生物, 分别命名为 eutypellarins A 和 B (1 和 2), 以及两个已知的异戊二烯取代苯甲醛衍生物(3 和 4). 通过高分辨质谱、核磁共振波谱以及量子化学计算对新化合物的结构进行确定. 首次从弯孢聚壳属真菌中发现异戊二烯取代二氢异香豆素和色烯酰胺衍生物. 采用 2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸(ABTS)自由基清除法和铁离子还原(FRAP)法对所有化合物进行总抗氧化能力的测定. 结果显示化合物 1 和 4 具有中等的抗氧化效果, 其 Trolox 等效抗氧化能力分别为(0.51±0.016)和(0.76±0.007).

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“…[16] On the other hand, amides are nitrogen-containing derivatives of carboxylic acids. Amide derivatives play a significant role in pesticide and pharmaceutical industries because of their rich biological activities, including anti-inflammatory, [17] insecticidal, [18,19] herbicidal, [20] antifungal, [21,22] and anticancer activities. [23] Also, thiourea derivatives are widely applied in medicine and agriculture because they hold various biological activities, [24] like antifungal, [25 -27] herbicidal, [28] anti-inflammatory, [29,30] antibacterial, [31] antiviral, [32] and plant growth regulation [33,34] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antifungal Activity and 3D‐QSAR Study of Novel Anisaldehyde‐Derived Amide‐Thiourea Compounds

Duan

et al. 2022

Chemistry & Biodiversity

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Succinate dehydrogenase (SDH) is an important target enzyme for designing agricultural chemical fungicides. In order to explore novel natural product‐based antifungal agents, twenty‐one unreported anisaldehyde‐derived amide‐thiourea compounds were designed and synthesized using the principle of active splicing, and structurally confirmed by 1H‐NMR, 13C‐NMR, ESI‐MS, FT‐IR, and element analysis. In vitro antifungal activity of the target compounds was evaluated by the agar dilution method. The results showed that some target compounds exhibited better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compounds 5c, 5o, and 5r displayed excellent antifungal activity of 92.6 %, 92.6 % and 99.1 % against P. piricola, respectively, better than that of the positive control. In addition, 3D‐QSAR analysis was carried out by the CoMFA method to reveal the relationship between the structures of the target compounds and their inhibitory activities. The simulative binding mode of the target compounds and SDH was also studied by molecular docking.

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Synthesis and anti-inflammatory activity evaluation of novel chroman derivatives

Abstract: In an effort to develop potent anti-inflammatory agents, a series of novel chroman derivatives including acyclic amidochromans, chromanyl esters and chromanyl acrylates have been designed, synthesized and fully characterized. These...

Cited by 9 publications

References 24 publications

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents

Study on Secondary Metabolites of Marine-Derived Fungus Eutypella sp. F0219

Synthesis, Antifungal Activity and 3D‐QSAR Study of Novel Anisaldehyde‐Derived Amide‐Thiourea Compounds

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