Cytotoxic Activity of Indonesian Pogonatum neesii Dozy from Cibodas Botanical Garden: In Silico Molecular Docking and In Vitro Evaluation

IF 1.4 Q4 PHARMACOLOGY & PHARMACY
Rizky Nurdiansyah, Agus Budiawan Naro Putra, Ainun Nadhifah, Erika Chriscensia, Ulung Khoe Gondo Kusumo, Stephanie Angela Yosiano, Anastasia Beatrix Musung, Sintikhe A Wenas, Steve Makalew, Patricia Lovina, Intani Quarta Lailaty, Fransisca Aurelia Rahmad, Fandi Sutanto, Pietradewi Hartrianti
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Abstract

Background: The exploration of bryophytes biodiversity in Indonesia due to its abundance and the bioactivity of its phytochemical content, such as alkaloids and polyphenols, has received increased interest. Despite some species proven to possess pharmacological properties, the antiproliferative study of Indonesian native moss, such as the Pogonatum genus, is limited. Hence, this study aims to evaluate the anticancer effects of Pogonatum neesii Dozy antiproliferative activity on colon and cervical cancer through in silico and in vitro methods. Methods: Molecular docking analysis using Autodock VINA in PyRx softwre was conducted between natural compounds found on P. neesii and several target proteins, DNA (cytosine-5)- methyltransferase 1 (DMT-1) (Protein Data Bank (PDB) id: 4WXX) in colon cancer and B-cell lymphoma 2 (Bcl-2) (PDB id: 4LXD) in cervical cancer. Afterwards, total phenolic and alkaloid contents were measured. Subsequently, P. neesii was tested on HaCaT (keratinocytes), HEK293 (human embryonic kidney), HT-29 (colorectal cancer models) and HeLa (cervical cancer model) to observe its cytotoxicity. Results: Out of eight compounds, chlorogenate was found to exert the best binding energy with target proteins, although it had lower binding affinity than the protein’s natural ligand. However, the biological, drug-likeness, and toxicity analysis suggested the drug potency of the compound, thus we did the in vitro analysis. P. neesii showed significant cytotoxic effects on HT-29 and HeLa cells, while it did not exert any cytotoxic effects on HaCaT and HEK-293 cells, at the same concentrations. Conclusion: P. neesii has been shown to have the potential as an anticancer agent through in silico and in vitro analysis, where the extract showed selective cytotoxicity towards cancer cell lines and cytocompatibility towards normal cell lines. Chlorogenate was pinpointed as the compound with the most activity and interaction with the target proteins in both cancers.
印尼木竹的细胞毒活性:硅分子对接及体外评价
背景:印度尼西亚苔藓植物多样性的探索由于其丰富的植物化学成分,如生物碱和多酚的生物活性,已受到越来越多的兴趣。尽管一些物种被证明具有药理特性,但对印度尼西亚本地苔藓(如Pogonatum属)的抗增殖研究是有限的。因此,本研究旨在通过实验和体外方法,探讨黄精对结肠癌和宫颈癌的抗增殖作用。方法:利用PyRx软件中的Autodock VINA软件,对neesii上发现的天然化合物与结肠癌中的DNA(胞嘧啶-5)-甲基转移酶1 (DMT-1)(蛋白数据库(PDB) id: 4WXX)和宫颈癌中的b细胞淋巴瘤2 (Bcl-2) (PDB id: 4LXD)等靶蛋白进行分子对接分析。然后测定总酚和生物碱含量。随后,对HaCaT(角化细胞)、HEK293(人胚胎肾)、HT-29(结直肠癌模型)和HeLa(宫颈癌模型)进行细胞毒性检测。结果:在8种化合物中,绿原酸与靶蛋白的结合能最好,但其结合亲和力低于靶蛋白的天然配体。然而,生物学、药物相似性和毒性分析表明该化合物具有药物效力,因此我们进行了体外分析。在相同浓度下,P. neesii对HT-29和HeLa细胞有明显的细胞毒作用,而对HaCaT和HEK-293细胞无明显的细胞毒作用。结论:通过体外和室内实验分析表明,该提取物对癌细胞具有选择性细胞毒性,对正常细胞株具有细胞相容性。在这两种癌症中,绿原酸被确定为最具活性和与目标蛋白相互作用的化合物。
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来源期刊
Pharmaceutical Sciences
Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
CiteScore
2.60
自引率
5.90%
发文量
38
审稿时长
4 weeks
期刊介绍: Pharmaceutical Sciences provides a forum for the publication of original research articles, reviews, short communications, and editorials (by invitation only) in all areas of pharmaceutical sciences, including these topics: Clinical Pharmacy Medicinal and Pharmaceutical Chemistry Pharmaceutical Analysis Pharmaceutics Pharmacognosy Pharmacology and Toxicology Pharmaceutical Biotechnology Pharmaceutical Nanotechnology Pharmacoeconomy Radiopharmacy Water, Food, Drug and Cosmetic Control.
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