INSILICO STUDIES OF SULFUR-CONTAINING SHIKONIN OXIME DERIVATIVES AS INHIBITORS OF MGC 803 GASTRIC CANCER CELL LINE
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https://doi.org/10.18540/jcecvl5iss1pp0079-0089Palavras-chave:
Keywords, QSAR, Molecular docking, Shikonin oxime, Density Functional Theory, Genetic Function Algorithm.Resumo
Quantitative structural activity relationship and molecular docking studies were performed to predict the anticancer activity of 41 sulfur-containing shikonin oxime derivatives. Quantum chemical calculations method (Density Functional Theory with B3LYP/6-31G* basis set) were used in optimising the studied molecules to find the lowest geometry. Genetic function algorithm was employed in selecting five relevent molecular descriptors that derived a quantitative relationship between the anticancer activity and the structural properties of the studied compounds. Based on the value of coefficient of correlation R2 0.833, R2ext value of 0.64 R2adj value of 0.799 and Q2 value of 0.737, the model was found to be robust, highly satisfactory and predictive. Docking study between the derivatives of sulfur- containing shikonin oxime and fibroblast growth factor receptor (5A46) revealed that compound number 24 has the highest binding energy of -9.3 kcal/mol and all the other compounds has favourable binding affinity toward the target receptor.
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ADEDIRIN, O; UZAIRU, A; SHALLANGWA, G.A; ABECHI, S.E. QSAR studies on derivatives of quinazoline-4(3H)-ones with anticonvulsant activities. The journal of engineering and exact sciences JCEC, Vol 04 N. 02 (2018).
ARTHUR, D; UZAIRU, A; MAMZA, P; ABECHI, S; SHALLANGWA G. In silico modeling of cytotoxic behavior of anti-leukemia compound on HL-60 cell line. Journal of the Turkish chemical society, section A: chemistry. 2016, 3(2):147-158.
BELLO, A.S; UZAIRU, A; SHALLANGWA, G.A; IBRAHIM, A. Insilico studies of some indole derivatives as anti-hepatitis c drug. Journal of engineering and exact sciences JCEC, Vol 04 N. 02 (2018).
CHANG, A.H; PARSONNET, J. (2010) Role of bacteria in oncogenesis. clinical microbiology reviews 23 (4):837-857. doi 10.1128/CMR.00012-10.
GONZALEZ, CA; SALA, N; ROKKAS, T; SALA, ROKKAS; (2013). Gastric cancer: epidemiologic aspects. Helicobacter. 18 (supplement 1): 34-38.
GUANG, H; HUI, Z; QING, M; QI-JING, Z; JIN-YUN, D; BAO-QUAN, Z; SHAO-SHUN, L. "Synthesis and biological evaluation of sulfur -containing shikonin oxime derivatives as potential antineoplastic agent". European journal of medicinal chemistry. 2017 nov 14. 143(2018) 166-181.
JAIN, S; GHATE, M; BHADORIYA, K; BARI, S; CHAUDHARI, A; BORSE, J. 2D, 3D QSAR and docking studies of 1, 2, 3 thiadiazole thioacetanilides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors Org Med Chem Lett, 2012;2:1
JANET, M; CASSIO, LYN; RICHARD M GLASS. Stomach cancer, JAMA network doi 10.1001/jama.30317.1771.
KENNARD, R,W; STONE, L.A. Computer aided design of experiments. Technometrics, 11(1), 137-148, 1969.
LI, YP; WENG, X; NING, FX; OU, J-B; HOU, J-Q; LUO, HB; HUANG, S-L. 3D QSAR studies of azaoxoisoaporphine, oxoaporphine and oxoisoaporphine derivatives as anti-AChE and anti-AD agents by the CoMFA method. j mol Graph Model, 2013 ;41:61-67.
RAVICHANDRAN, V; RAJAK, H; JAIN, A; SIVADASAN, S; VARGHESE, C.P; KISHORE-AGRAWAL, R. Validation of QSAR models-strategies and importance. International Journal of Drug Design and Discovery. 2011 July 01. 2 511–519.
ROY, K; SUPRATIC, K; RUDRA, N. Understanding the Basics of QSAR for Application in Pharmaceutical Sciences and Risk Assessment. 2015 April 3. chapter 10 pp 257-425.
RUDON, G; RAYMOND, W. (2007) Cancer biology (4th edition). Oxford university press. p. 223 ISBN 9780195175431.
SHILONG, YING; XIAOJING, DU; WEITAO, FU; DI, YUN; LIPING, CHEN; YUEPIAO, CAI; QING, XU; JIANZHANG, WU; WULAN, LI; GUANG, LIANG. Synthesis, biological evaluation, QSAR and molecular dynamics simulation studies of potential fibroblast growth receptor 1 inhibitors for treatment of gastric cancer. European journal of medicinal chemistry. volume 127, 15 February 2017, pages 885-899.
SHOLA, A.S; UBA, S; UZAIRU, A. Insilico study for investigating and predicting activities of 1,2,4-triazole derivatives as potent tubercular agents. The journal of engineering and exact sciences JCEC, vol. 04 N.02 (2018).
TODESCHINI, R; CONSONNI, V; GRAMATICA, P. Chemometrics in QSAR. Comprehensive chemometrics. ChemBiochem data anal, 2009; 4: 129-172.
YAP, C.W. PaDEL-descriptor: An open source software to calculate molecular descriptors and fingerprints. J. Comput. Chem, 2011. 32(7): p. 1466-1474.
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