Jatinangor, February 6th 2021. Breast cancer is recognized as the leading cause of cancer death among women in many Asian countries. In general, breast cancer in Indonesia ranks second in cancer in women and the leading cause of death. In 2018, there were 11.6% new cases of breast cancer with a death rate of 6.6%. Breast cancer is a disease in which cells in the breast tissue change and divide uncontrollably, usually producing a lump or a mass. Most breast cancers begin in the lobules or ducts that connect the lobules to the nipple. Breast cancer is a cancer caused by uncontrolled growth of cells in the breast tissue. One common trigger in breast cancer is overexpression of alpha receptor (ERα) estrogens. Compounds isolated from natural materials as breast anticancer have been developed. In previous studies, 2 ‘, 4’-dihydroxy-6-methoxy-3,5-dimethylchalcone was isolated as an active compound from the leaves of Eugenia aquea to provide anticancer activity in the breast. This compound has been tested for its inhibitory activity against MCF-7 cells using a proliferation assay and its ability to induce apoptotic mechanisms, through activation of poly protein (ADP-ribose) polymerase (PARP), but has a poor IC50 of 270μM and 250μM on 24 and 48 hours of testing.
This inspired Riska Prasetiawati, a lecturer at the Faculty of Mathematics and Natural Sciences, Universitas Garut to conduct research on Modification of Chalcone Compounds to Obtain New Antiproliferative Compounds for Breast Cancer, which was presented at the Pharmacy Doctoral Promotion Session held at the Auditorium 2nd floor of Dean Building of the Faculty of Pharmacy, Padjadjaran University on Tuesday (2/2).
In Riska’s dissertation, Riska explained that currently, many natural materials have been found and known, which have activity as an anticancer and antibacterial source to be developed. Synthesis of compounds based on models from natural compounds is a natural medicine. The development and discovery of new drugs from natural ingredients that have the potential for chemotherapy can be done through the Computer Aided Drug Design (CADD) approach.
The development of research on cancer treatment seeks to increase its selectivity and safety and reduce side effects on normal cells. Increased science related to molecular mechanisms and the pathophysiology of cancer in humans encourages the development of anticancer drugs at molecular targets so that they are expected to produce anticancer drugs with greater effectiveness and lower toxicity. Therefore, the development of anti-cancer drugs needs to be done, including the use of drugs from natural ingredients. The use of medicines derived from natural or herbal ingredients has increased throughout the world, especially in developing countries. Besides being cheap, the use of herbs to prevent and treat various diseases is more easily accepted by the body with minimal side effects.
The use of these medicinal plants is often developed based on their empirical use or based on ethnobotanical studies. Scientific evidence regarding the safety and effectiveness of therapeutics with herbal products can strengthen their use as an alternative to modern medicine.
The use of herbal medicines for cancer has also increased, around 7-48% of patients who have been diagnosed with cancer use herbal medicines. This has led to demands for herbal products that have controlled quality in terms of their content and pharmacological effects. Most of the research on medicinal plants has been directed at a better understanding of their pharmacological effects in addition to their phytochemical studies.
There have been many developments of anti-cancer drugs derived from natural ingredients. One that has been discovered is a chalcone compound derived from Eugenia aquea, namely 2′,4′-dihydroxy-6-methoxy-3,5-dimethylchalcone. This chalcone derivative compound has similarities with the structure of tamoxifen, but has a poor IC50, namely 270μM and 250μM on the 24 and 48 hour tests against MCF7 cell lines and 142.58μM against T47D cell lines so it is necessary to optimize these compounds.
In her research, Riska carried out molecular modification of chalcone derivatives to obtain compounds that have better anticancer activity with low toxicity. As the initial stage in this research is to design a modified compound of chalcone. Many recent studies have explored pyrazoline from various pharmacological aspects. A broad pharmacological profile has been shown by pyrazoline. Pyrazoline is a widely studied nitrogen heterocyclic compound. The rings are stable so that scientists in chemistry are interested in modifying the structure of the rings.
Second stage, In silico tests are carried out included virtual screening using pharmacophores, molecular docking studies, molecular dynamics simulations, absorption predictions, distribution and toxicity to tamoxifen, chalcone derivatives and compounds modified by chalcone.
The next step is to synthesize the modified chalcone compound which is predicted to have better activity based on the in silico study. The synthesized compounds were characterized using TLC, IR spectroscopy, 1H-NMR and HRMS.
The final stage in this research is to test the anticancer activity of the breast using the MTT antiproliferation assay method.
From the results of this study, Riska succeeded in synthesizing new compounds of pyrazoline derivatives, namely Modifina12, 13 and Modifina14, which are modified results of chalcone compounds and proven to have antiproliferative activity against MCF-7 cells and are predicted to have minimal side effects.
This doctoral session was led by Prof. Dr. Ajeng Diantini M.Si with the Secretary of the Session Dr. Aliya Nur Hasanah M.Si. Chief Promoter Prof.Muchtaridi Ph.D. While the members of the promoter team consisted of prof. Dr. Adel Zamri DEA and Dr. Med Sc Melisa Intan B. The expert opponent team consisted of drg. Ferry Sandra Ph.D from PT. Prodia, dr. Ronny Lesmana MD.M.Kes, AIFO, Ph.D from Unpad, Dr. Ida Musfiroh M.Si from Unpad and Prof.Dr. Anas Subarnas M.Sc as the representative of Unpad Professor * (wep)