Design Anticancer Potential of Zn(II)Isoleucinedithiocarbamate Complex on MCF-7 Cell Lines: Synthesis, Characterization, Molecular Docking, Molecular Dynamic, ADMET, and In-Vitro Studies Rizal Irfandi(a,b), Indah Raya(c*), Ahyar Ahmad(c), Ahmad Fudholi(d,e), Riswandi(c), Santi Santi(f), Wynda Puspa Azalea(g), Suriati Eka Putri(h), Samuel Olawale Olubode(i)
a)Doctoral Program, Department of Chemistry, Faculty of Mathematics, and Natural Science, Hasanuddin University, Makassar 90245, Indonesia
b)Department of Biology Education, Faculty of Teacher Training and Education, Universitas Puangrimaggalatung, Sengkang 90915, Indonesia
c)Department of Chemistry, Faculty of Mathematics, and Natural Science, Hasanuddin University Makassar 90245, Indonesia
*indahraya[at]unhas.ac.id
d)Solar Energy Research Institute, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor 43600, Malaysia
e)Research Centre for Electrical Power and Mechatronics, Institute of Science (LIPI), Bandung, Indonesia g Research Center of Smart Molecules and Natural Genetic Resources, Brawijaya University, Malang, Indonesia
f)Medical Laboratory Technology, Faculty of Health Technology, Megarezky University, Makassar 90234, Indonesia
g)OKU Selatan District Health Office, Faculty of Pharmacy Pancasila University Jakarta 12620, Indonesia
h)Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Makassar, Makassar, Jalan Daeng Tata Raya Makassar, 90244, Indonesia
i)Department of Biochemistry, Adekunle Ajasin University Akungba Akoko, Ondo State, Nigeria.
Abstract
Cisplatin which is commonly used today as a cancer drug, still leaves some problems such as showing toxic properties in the body. New complex has been designed as a potential anticancer drug candidate by minimizing its toxic properties to the body. The complex synthesis method was carried out in situ by mixing the ingredients in one step, namely ZnCl2 and isoleucineditiocarbamate in a ratio of 3:5 mmol. The Zn complexes were characterized by UV Vis spectroscopy, FTIR, determination of melting point, conductivity, and HOMO LUMO were studied. Computational NMR spectrum analysis was performed. Molecular docking results of Zn Isoleucinedithiocarbamate against HIF1 showed that the Zn complex was a good HIF1 inhibitor by showing a docking score of 6.6, having hydrogen bonds with ARG 17, VAL264 and GLU15. Also having alkyl bonds with TRP27 ans LEU32, and Pi-Alkyl bonds with PRO41 and ARG44. The mechanism of action of the active representative compounds was identified by molecular dynamics simulation. Anticancer potency of Zn isoleucinedithiocarbamate against MCF7 cells at an IC50 value of 362.70 gmL showed changes in cancer cell morphology. Zn(II) Isoleucineedithiocarbamate complex has potential as an anticancer compound because it has a significant inhibitory effect on breast cancer cells (MCF7). Based on the study ADMET has characteristics like a good drug with lower toxicity.
Keywords: Dithiocarbamate, Zn(II), Isoleucine, In-vitro, ADMET, cancer
