Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti-inflammatory and antioxidant agents
Synthesis and biological evaluation of simple methoxylated chalcones as anticancer, anti-inflammatory and antioxidant agents
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DOI：
10.1016/j.bmc.2009.11.066
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发表时间：
2010-02-01
影响因子：
3.5
通讯作者：
Khobragade, Chandrahas N.
中科院分区：
文献类型：
--
作者：
Bandgar, Babasaheb P.;Gawande, Shrikant S.;Khobragade, Chandrahas N.
查耳酮是一类具有细胞毒性、抗炎和抗氧化作用的化合物。本研究通过Claisen-Schmidt缩合反应合成了结构简单的甲氧基查尔酮化合物，并对其生物活性进行了评价。化合物的结构经IR、1HNMR和质谱确证。数据显示，与标准flavopiridol和吉西他滨（在700 nM和500 nM浓度下分别为70-90%）相比，化合物3s（在10 μ M浓度下为99-100%）完全抑制所选的五种人癌细胞系，随后是3a、3 n、3 o、3 p、3q、3r。在测试的化合物中，3l、3 m、3r和3s显示出有希望的抗TNF-α和IL-6的抗炎活性，在10 μ M浓度下具有90-100%的抑制。化合物3 o、3 n、3l、3r、3 m、3a、3 p、3c和3s在1 mM浓度下具有DPPH自由基清除活性。总体而言，3s作为先导化合物具有良好的抗癌，抗炎和抗氧化活性。通过体外细胞毒性试验验证了化合物的生物利用度，证实其无毒。构效关系（SAR）和计算机模拟药物相关性质（HBDs、C2 H4、PSA、c Log P、电离势、分子量、E（HOMO）和E（LUMO））进一步证实了这些化合物是未来药物发现研究的潜在候选者。(C)2009爱思唯尔有限公司保留所有权利。
Chalcones have been identified as interesting compounds with cytotoxicity, anti-inflammatory and antioxidant properties. In the present study, simple methoxychalcones were synthesized by Claisen-Schmidt condensation reaction and evaluated for above biological activities. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. The data revealed that compound 3s (99-100% at 10 mu M concentration) completely inhibit the selected five human cancer cell lines as compared to standard flavopiridol and gemcitabine (70-90% at 700 nM and 500 nM concentrations, respectively), followed by 3a, 3n, 3o, 3p, 3q, 3r. Among the tested compounds 3l, 3m, 3r, and 3s exhibited promising anti-inflammatory activity against TNF-alpha and IL-6 with 90-100% inhibition at 10 mu M concentration. DPPH free radical scavenging activity was given by the compounds 3o, 3n, 3l, 3r, 3m, 3a, 3p, 3c and 3s at 1 mM concentration. Overall, 3s was obtained as lead compound with promising anticancer, anti-inflammatory and antioxidant activities. Bioavailability of compounds were checked by in vitro cytotoxicity study and confirmed to be nontoxic. The structure activity relationship (SAR) and in silico drug relevant properties (HBDs, HBAs, PSA, c Log P, ionization potential, molecular weight, E(HOMO) and E(LUMO)) further confirmed that the compounds were potential candidates for future drug discovery study. (C) 2009 Elsevier Ltd. All rights reserved.