Berberine as Source of Antiproliferative Hybrid Compounds: In Vitro Antiproliferative Activity and Quantitative Structure-activity Relationship

小檗碱 赫拉 异喹啉 生物碱 化学 生物化学 脂肪酸 癌细胞 体外 细胞培养 细胞毒性 MTT法 立体化学 癌症 生物 遗传学
作者
Mario Alberto Leyva-Peralta,Ramón Enrique Robles‐Zepeda,Rodrigo Said Razo‐Hernández,Laura Patricia Alvarez Berber,Karen Ochoa Lara,Eduardo Ruíz-Bustos,J.C. Galvez-Ruiz
出处
期刊:Anti-cancer Agents in Medicinal Chemistry [Bentham Science Publishers]
卷期号:19 (15): 1820-1834 被引量:13
标识
DOI:10.2174/1871520619666190503121820
摘要

Background: Despite advances for cancer treatment, it still remains a major worldwide public health problem. Compounds derived from natural sources are important alternatives to combat this mortal disease. Berberine is an isoquinoline alkaloid with a wide variety of pharmacological properties, including antiproliferative activity. Previously, we have found that fatty acids also show antiproliferative activity against cancer cell lines. Background: Despite advances for cancer treatment, it still remains a major worldwide public health problem. Compounds derived from natural sources are important alternatives to combat this mortal disease. Berberine is an isoquinoline alkaloid with a wide variety of pharmacological properties, including antiproliferative activity. Previously, we have found that fatty acids also show antiproliferative activity against cancer cell lines. Objective: To combine berberine and fatty acids, or carboxylic acids, in order to improve their antiproliferative properties. Objective: To combine berberine and fatty acids, or carboxylic acids, in order to improve their antiproliferative properties. Methods: We synthetized six new hybrid derivatives through a simple methylenedioxy group-cleavage method followed by the reaction with fatty acids, or carboxylic acids. The structure of the compounds was elucidated by IR, NMR and HRMS. The in vitro antiproliferative activity against four human cancer cell lines (HeLa, A-549, PC-3 and LS-180) and one normal cell line (ARPE-19), was evaluated by the MTT method. Chemical structures were drawn using SPARTAN '08 software and the conformational analysis was carried out with a molecular mechanic level of theory and the SYBIL force field. All molecular structures were subjected to geometrical optimization at the semi-empirical method PM3. Molecular descriptors were calculated using DRAGON 5.4 and SPARTAN ´08 programs. Methods: We synthetized six new hybrid derivatives through a simple methylenedioxy group-cleavage method followed by the reaction with fatty acids, or carboxylic acids. The structure of the compounds was elucidated by IR, NMR and HRMS. The in vitro antiproliferative activity against four human cancer cell lines (HeLa, A-549, PC-3 and LS-180) and one normal cell line (ARPE-19), was evaluated by the MTT method. Chemical structures were drawn using SPARTAN '08 software and the conformational analysis was carried out with a molecular mechanic level of theory and the SYBIL force field. All molecular structures were subjected to geometrical optimization at the semi-empirical method PM3. Molecular descriptors were calculated using DRAGON 5.4 and SPARTAN ´08 programs. Results: The geranic acid and berberine hybrid compound (6) improved the antiproliferative activity shown by natural berberine, even more than the 16- to 18-carbon atoms fatty acids. Compound 6 showed IC50 values of 2.40 ± 0.60, 1.5 ± 0.24, 5.85 ± 1.07 and 5.44 ± 0.24 μM, against HeLa, A-549, PC-3 and LS-180 human cancer cell lines, respectively. Using this information, we performed a quantitative structure-activity relationship (QSAR) of the hybrid molecules and found that the molecular descriptors associated with the antiproliferative activity are: hydrophobic constant associated with substituents (!(!) = 6.5), molecular volume descriptor (!"#!"#$%& ≈ 700 Å!), !!"#", number of rotatable bonds (!"#) and number of 6-membered rings (!"06). Results: The geranic acid and berberine hybrid compound (6) improved the antiproliferative activity shown by natural berberine, even more than the 16- to 18-carbon atoms fatty acids. Compound 6 showed IC50 values of 2.40 ± 0.60, 1.5 ± 0.24, 5.85 ± 1.07 and 5.44 ± 0.24 μM, against HeLa, A-549, PC-3 and LS-180 human cancer cell lines, respectively. Using this information, we performed a quantitative structure-activity relationship (QSAR) of the hybrid molecules and found that the molecular descriptors associated with the antiproliferative activity are: hydrophobic constant associated with substituents (!(!) = 6.5), molecular volume descriptor (!"#!"#$%& ≈ 700 Å!), !!"#", number of rotatable bonds (!"#) and number of 6-membered rings (!"06). Conclusion: The methylendioxy and methoxyl groups in berberine are important for the antiproliferative activity shown by its derivatives. Better results in antiproliferative activity were obtained in compound 6 with the prenyl moiety. The QSAR indicates that the molecular descriptors which associated positively with the antiproliferative activity are: hydrophobic constant associated with substituents (! ! = 6.5), molecular volume descriptor (!"#!"#$%& ≈700 Å3) and !!"#". This research gave the basis for the design and preparation of new, easily afforded molecules derived from berberine and carboxylic acids, with improved antiproliferative activity. Conclusion: The methylendioxy and methoxyl groups in berberine are important for the antiproliferative activity shown by its derivatives. Better results in antiproliferative activity were obtained in compound 6 with the prenyl moiety. The QSAR indicates that the molecular descriptors which associated positively with the antiproliferative activity are: hydrophobic constant associated with substituents (! ! = 6.5), molecular volume descriptor (!"#!"#$%& ≈700 Å3) and !!"#". This research gave the basis for the design and preparation of new, easily afforded molecules derived from berberine and carboxylic acids, with improved antiproliferative activity.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
领导范儿应助Nozomi采纳,获得10
刚刚
小马甲应助YJ888采纳,获得10
刚刚
香蕉觅云应助jialiu采纳,获得10
刚刚
cosmos完成签到,获得积分10
1秒前
大个应助独特乘云采纳,获得10
2秒前
2秒前
小晓发布了新的文献求助10
2秒前
wonder123发布了新的文献求助10
4秒前
老实起哞完成签到,获得积分10
4秒前
6秒前
7秒前
gsj发布了新的文献求助10
8秒前
9秒前
所所应助wonder123采纳,获得10
9秒前
10秒前
10秒前
10秒前
田様应助忆茶戏采纳,获得10
10秒前
wss完成签到,获得积分10
11秒前
11秒前
11秒前
song_song发布了新的文献求助10
12秒前
桐桐应助贪玩的野狍子采纳,获得50
12秒前
路小黑发布了新的文献求助10
13秒前
wss发布了新的文献求助10
13秒前
UsihaGuwalgiya完成签到,获得积分10
14秒前
14秒前
15秒前
独特乘云发布了新的文献求助10
15秒前
16秒前
yyyyxxxg完成签到,获得积分10
17秒前
18秒前
健壮的花生zzz完成签到,获得积分10
19秒前
19秒前
Michael-布莱恩特完成签到,获得积分10
20秒前
323431完成签到,获得积分10
21秒前
烟花应助郭小宝采纳,获得10
21秒前
lzx发布了新的文献求助10
22秒前
LJF完成签到,获得积分10
23秒前
量子星尘发布了新的文献求助10
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989444
求助须知:如何正确求助?哪些是违规求助? 3531531
关于积分的说明 11254250
捐赠科研通 3270191
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174