Author(s): Elizabeth Divina, Linda Erlina, Khaerunissa Anbar Istiadi, Elfa Siska Yasa Putri, Fadilah Fadilah

Email(s): fadilah81@gmail.com

DOI: 10.52711/0974-360X.2022.00773   

Address: Elizabeth Divina1, Linda Erlina2,3, Khaerunissa Anbar Istiadi3, Elfa Siska Yasa Putri4, Fadilah Fadilah2,3*
1Faculty of Medicine, University of Indonesia, Salemba Raya 6, Jakarta, Indonesia
. 2Department of Medical Chemistry, Faculty of Medicine, University of Indonesia, Salemba Raya 6, Jakarta, Indonesia.
3Bioinformatics Core Facilities, IMERI Faculty of Medicine, University of Indonesia, Salemba Raya 6, Jakarta, Indonesia.
4Faculty of Pharmacy and Science, Muhammadiyah Prof. Dr. Hamka University, Jakarta, Indonesia.
*Corresponding Author

Published In:   Volume - 15,      Issue - 10,     Year - 2022


ABSTRACT:
Cancer is a major health concern in both developed and developing countries, second leading cause of mortality worldwide. Among the different types of cancer, breast cancer is the most common cancer found in females worldwide. Studies have shown that salicylic acid decreases cell viability and potentially used in cancer therapy. This research aim is to analyze the cytotoxicity effect of alkylated salicylic acid towards breast cancer cells T47D. Samples used are methyl salicylate, ethyl salicylate, butyl salicylate, isoamyl salicylate, and octyl salicylate. Thin layer chromatography was done to samples and MTT test was done against T47D cancer cells to obtain cancer cell growth and IC50 value. QSAR analysis were carried out to predict the theoretical activity of the alkylated salicylates. Based on MTT result, there was shown an increase of cytotoxicity effect with higher concentration. IC50 value of alkylated salicylic acid showed more significant cytotoxicity effect (p<0,05) when compared to IC50 value of salicylic acid, except octyl salicylate. This shows that addition of alkyl group enhances cytotoxicity effect of salicylic acid due to increase of affinity. The IC50 value of alkylated salicylic acid showed lower results compared to salicylic acid. The QSAR equation is Log (1/IC50) = -1236.21871 - 236.42806 *logP(o/w) -1186.53810 * AM1_LUMO +251.55826* mr ((n = 7 r = 0,94 RMSE = 4,08). The QSAR showed the descriptors which has effect towards inhibition activity of breast cancer cell line are log P, mr, and AM_1LUMO.


Cite this article:
Elizabeth Divina, Linda Erlina, Khaerunissa Anbar Istiadi, Elfa Siska Yasa Putri, Fadilah Fadilah. QSAR and Anticancer effect of Alkyl salicylate on Breast cancer T47D Cells Lines. Research Journal of Pharmacy and Technology 2022; 15(10):4607-3. doi: 10.52711/0974-360X.2022.00773

Cite(Electronic):
Elizabeth Divina, Linda Erlina, Khaerunissa Anbar Istiadi, Elfa Siska Yasa Putri, Fadilah Fadilah. QSAR and Anticancer effect of Alkyl salicylate on Breast cancer T47D Cells Lines. Research Journal of Pharmacy and Technology 2022; 15(10):4607-3. doi: 10.52711/0974-360X.2022.00773   Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2022-15-10-46


REFERENCES:
1.    Organization WH. The Global Cancer Observatory: Indonesia [Internet]. 2019 [cited 2019 Jun 30]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf
2.    Dange VN, Shid SJ, Magdum CS, Mohite SK. A Review on Breast cancer: An Overview. Asian J Pharm Res. 2017;7(1):49. doi.org/10.5958/2231-5691.2017.00008.9
3.    Yadav AR, Mohite SK. Cancer-A silent killer: An overview. Asian J Pharm Res. 2020;10(3):213. doi.org/10.5958/2231-5691.2020.00036.2
4.    Sudarshan B, Vikas S, Viveknand C, Vilas S, Suresh R, Ganesh D. Tamoxifen Citrate Loaded Solid Lipid Nanoparticles- A Novel Approach In The Treatment of ER+ Breast Cancer. Res J Pharm Dos Forms Technol. 2009;1(2):143–9.
5.    Nazarali SA, Narod SA. Tamoxifen for women at high risk of breast cancer. Breast cancer (Dove Med Press. 2014;6:29–36. doi.org/10.2147/BCTT.S43763
6.    Arjun P, S.C. S, Ateneriya U, Choudhary S. A Comprehensive Review on Breast Cancer. Asian J Nurs Educ Res. 2012;2(1):28–32. doi.org/10.5958/2349-2996
7.    Tao JJ, Visvanathan K, Wolff AC. Long term side effects of adjuvant chemotherapy in patients with early breast  cancer. Breast. 2015;24 Suppl 2(0 2):S149-53. doi.org/10.1016/j.breast.2015.07.035
8.    Jacob R, Aswathy AB, Sivadas A. Prospective randomized case control study of oral aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV). Res J Pharm Technol. 2016;9(12):2180. doi.org/10.5958/0974-360x.2016.00441.8
9.    MIYOSHI JUN, YAJIMA T, SHIMAMURA K, MATSUOKA K, OKAMOTO S, HIGUCHI H, et al. 5-Aminosalicylic Acid Mediates Expression of Cyclooxygenase-2 and 15-Hydroxyprostaglandin Dehydrogenase to Suppress Colorectal Tumorigenesis. Anticancer Res. 2012;32(4):1193 LP – 1202.
10.    Rousseaux C, El-Jamal N, Fumery M, Dubuquoy C, Romano O, Chatelain D, et al. The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ. Carcinogenesis. 2013;34(11):2580–6. doi.org/10.1093/carcin/bgt245
11.    Ryan BM, Russel MG, Langholz E, Stockbrugger RW. Aminosalicylates and colorectal cancer in IBD: a not-so bitter pill to swallow. Am J Gastroenterol. 2003;98(8):1682—1687. doi.org/10.1111/j.1572-0241.2003.07599.x
12.    Howe LR. Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 2007;9(4):210. doi.org/10.1186/bcr1678
13.    Bhasker S, Sandeep G, Ranganath Y. Future of Cancer Therapy-COX-2 Inhibitors: A Review. Res J Pharm Technol. 2009;2(4):2009. doi.org/10.5958/0974-360X
14.    Radde BN, Alizadeh-Rad N, Price SM, Schultz DJ, Klinge CM. Anacardic Acid, Salicylic Acid, and Oleic Acid Differentially Alter Cellular  Bioenergetic Function in Breast Cancer Cells. J Cell Biochem. 2016;117(11):2521–32. doi.org/10.1002/jcb.25544
15.    Radde BN, Ivanova MM, Mai HX, Salabei JK, Hill BG, Klinge CM. Bioenergetic differences between MCF-7 and T47D breast cancer cells and their  regulation by oestradiol and tamoxifen. Biochem J. 2015;465(1):49–61. doi.org/10.1042/BJ20131608
16.    Vejselova D, Kutlu H. Inhibitory effects of salicylic acid on A549 human lung adenocarcinoma cell viability. Turkish J Biol. 2015;39:1–5. doi.org/10.3906/biy-1401-7
17.    Billones JB, Buenaobra S. Quantitative Structure-Activity Relationship (QSAR) Study of Cyclooxygenase-2 (COX-2) Inhibitors. Philipp J Sci. 2011;140(2):125–32.
18.    Fadilah F, Arsianti A, Yanuar A, Andrajati R, Paramita RI, Purwaningsih EH. Structure activity relationship analysis of antioxidant activity of simple benzene carboxylic acids group, based on multiple linear regression. Orient J Chem. 2018;34(5):2656–60. doi.org/10.13005/ojc/340558
19.    Kawade VS, Kumbhar SS, Choudhari PB, Bhatia MS. 3D QSAR and Pharmacophore Modelling of some Pyrimidine Analogs as CDK4 Inhibitors. Asian J Res Chem. 2015;8(4):231. doi.org/10.5958/0974-4150.2015.00040.1
20.    E R, A S. High-performance thin-layer chromatography. New York: Thieme; 2007. 264 p.
21.    Kuswanti N, Widyarti S, Widodo W, Rifa’i M. Cytotoxicity of ethanolic extract of plumeria rubra L. Stem bark to cancer cells and lymphocytes. Res J Pharm Technol. 2018;11(12):5545–50. doi.org/10.5958/0974-360X.2018.01009.0
22.    Soni A, Femida P, Sharma P. In-vitro cytotoxic activity of plant saponin extracts on breast cancer cell-line. Res J Pharmacogn Phytochem. 2017;9(1):17. doi.org/10.5958/0975-4385.2017.00003.6
23.    Sasikala M, Sundaraganapathy R, Mohan S. MTT assay on anticancer properties of phytoconstituents from ipomoea aquatica forsskal using MCF–7 cell lines for breast cancer in women. Res J Pharm Technol. 2020;13(3):1356–60. doi.org/10.5958/0974-360X.2020.00250.4
24.    US National Library of Medicine. Methyl Salicylate [Internet]. PubChem Database. [cited 2020 Jan 7]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Methyl-salicylate
25.    US National Library of Medicine. Ethyl Salicylate. PubChem Database.
26.    US National Library of Medicine. Isoamyl Salicylate. PubChem Database.
27.    US National Library of Medicine. Butyl Salicylate. PubChem Database.
28.    National Center for Biotechnology Information. PubChem Compound Summary for CID 62624, Octyl salicylate. 2020.
29.    Hasl T, Jiricek I. The Prediction of Heat Storage Properties by the Study of Structural Effect on Organic Phase Change Materials. Energy Procedia. 2014;46:301–9. doi.org/https://doi.org/10.1016/j.egypro.2014.01.186
30.    Krippendorff B-F, Lienau P, Reichel A, Huisinga W. Optimizing classification of drug-drug interaction potential for CYP450 isoenzyme  inhibition assays in early drug discovery. J Biomol Screen. 2007;12(1):92–9. doi.org/10.1177/1087057106295897
31.    Atjanasuppat K, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, et al. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants  from Thailand. J Ethnopharmacol. 2009;123(3):475–82. doi.org/10.1016/j.jep.2009.03.010
32.    Ekinci D, Sentürk M, Küfrevioğlu Öİ. Salicylic acid derivatives: synthesis, features and usage as therapeutic tools. Expert Opin Ther Pat. 2011;21(12):1831–41. doi.org/10.1517/13543776.2011.636354
33.    Totzke G, Schulze-Osthoff K, Jänicke RU. Cyclooxygenase-2 (COX-2) inhibitors sensitize tumor cells specifically to death receptor-induced apoptosis independently of COX-2 inhibition. Oncogene. 2003;22(39):8021–30. doi.org/10.1038/sj.onc.1206837
34.    Kochel TJ, Goloubeva OG, Fulton AM. Upregulation of Cyclooxygenase-2/Prostaglandin E2 (COX-2/PGE2) Pathway Member  Multiple Drug Resistance-Associated Protein 4 (MRP4) and Downregulation of Prostaglandin Transporter (PGT) and 15-Prostaglandin Dehydrogenase (15-PGDH) in Triple-Negative Breas. Breast Cancer (Auckl). 2016;10:61–70. doi.org/10.4137/BCBCR.S38529
35.    Moselmani F, Al-Saleh J. Relation between Serum cyclo oxygenase-2 values and Tumor characteristics in breast cancer patients. Res J Pharm Technol [Internet]. 2020 [cited 2021 Mar 5];13(9):4320. Available from: https://rjptonline.org/AbstractView.aspx?PID=2020-13-9-51
36.    Stromgaard K, Krogsgaars-Larsen P, Madsen U. Textbook of Drug Design and Discovery [Internet]. 5th ed. Boca Raton: CRC Press; 2017 [cited 2021 Feb 24]. Available from: https://www.routledge.com/Textbook-of-Drug-Design-and-Discovery/Stromgaard-Krogsgaard-Larsen-Madsen/p/book/9781498702782
37.    SD S. Drug Design and Discovery : Methods and Protocols. New York: Humana Press; 2011. 284 p.
38.    Sproviero D, Julien S, Burford B, Taylor-Papadimitriou J, Burchell JM. Cyclooxygenase-2 enzyme induces the expression of the α-2,3-sialyltransferase-3  (ST3Gal-I) in breast cancer. J Biol Chem. 2012;287(53):44490–7. doi.org/10.1074/jbc.M112.427827
39.    Harris RE, Casto BC, Harris ZM. Cyclooxygenase-2 and the inflammogenesis of breast cancer. World J Clin Oncol. 2014;5(4):677–92. doi.org/10.5306/wjco.v5.i4.677
40.    Pang LY, Hurst EA, Argyle DJ. Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer Cells during Therapy. Sheng Z, editor. Stem Cells Int. 2016;2016:2048731. doi.org/10.1155/2016/2048731


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