Kolawole Oyebamiji Abel, Olatomide A Fadare, Banjo Semire
Department of Basic Sciences, Adeleke University, P.M.B. 250, Ede, Osun state, Nigeria.
Computational Chemistry Laboratory, Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology, P.M.B., 4000, Ogbomoso, Oyo State, Nigeria.
Heliyon. 2020 Mar 20;6(3):e03561. doi: 10.1016/j.heliyon.2020.e03561. eCollection 2020 Mar.
Gastric cancer as a dreaded disease which occurs in the digestive system of human being remain a threat to the medical world. Bioactivity of series of designed and synthesized molecular compounds containing triazole and pyrimidine moieties were subjected to quantum chemical calculations using B3LYP/6-31+G∗. The calculated molecular descriptors such as the E (eV), E (eV), band gap (eV), chemical hardness (η), global nucleophilicity, dipole moment (Debye), chemical potential, log P, molecular weight (amu) and Ovality. The descriptors that describe anti-gastric cancer activity of the studied compounds were used for QSAR analysis using SPSS and Gretl software packages for multiple linear regression (MLR), XLSTAT for partial least square (PLS) and MATLAB for artificial neural network (ANN). The methods (MLR, PLS, and ANN) were predictive. Nevertheless, ANN performed better than MLR and PLS. More so, molecular docking study was executed on the studied compounds and gastric cancer cell line (4oum); the docking studies showed that 2-(1-(2-(3-benzyl-5-(benzylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl)hydrazono)ethyl)phenol () having the lowest binding affinity (-8.40 kcal/mol); this was correlated to the observed inhibitory activity of the compound against gastric cancer. Thus, it showed better inhibition than other studied compounds. The amino acid residues that were involved in stabilizing in the active site of the are: VAL-9, ALA-10, THR-49, ASN-48, PRO-47 and TYR-46. Also, a good relationship was observed between the calculated binding affinity and the observed inhibition concentration (IC).
胃癌作为一种发生在人类消化系统的可怕疾病，仍然对医学界构成威胁。使用B3LYP/6-31+G∗对一系列含有三唑和嘧啶部分的设计和合成分子化合物的生物活性进行了量子化学计算。计算了分子描述符，如E（电子伏特）、E（电子伏特）、带隙（电子伏特）、化学硬度（η）、全局亲核性、偶极矩（德拜）、化学势、log P、分子量（原子质量单位）和椭圆率。使用SPSS和Gretl软件包进行多元线性回归（MLR）、XLSTAT进行偏最小二乘法（PLS）以及MATLAB进行人工神经网络（ANN），将描述所研究化合物抗胃癌活性的描述符用于QSAR分析。这些方法（MLR、PLS和ANN）具有预测性。然而，ANN的表现优于MLR和PLS。此外，对所研究的化合物和胃癌细胞系（4oum）进行了分子对接研究；对接研究表明，2-(1-(2-(3-苄基-5-(苄硫基)-3H-[1,2,3]三唑并[4,5-d]嘧啶-7-基)肼基)乙基)苯酚（）具有最低的结合亲和力（-8.40千卡/摩尔）；这与该化合物对胃癌的观察到的抑制活性相关。因此，它显示出比其他研究化合物更好的抑制作用。参与在的活性位点稳定的氨基酸残基为：VAL-9、ALA-10、THR-49、ASN-48、PRO-47和TYR-46。此外，在计算的结合亲和力和观察到的抑制浓度（IC）之间观察到了良好的关系。
