Abstract
AbstractPreviously, a series of pyridotriazolopyrimidines (1–6) were synthesized and fully described. The target compounds (1–6) were evaluated for their cytotoxicity against MCF-7, HepG2, WRL 68, and A549 (breast adenocarcinoma, hepatocellular carcinoma, embryonic liver, and pulmonary adenocarcinoma, respectively) cell lines using MTT assay. The tested compounds demonstrated cytotoxicity, but no significant activity. To elucidate the structure–cytotoxicity relation of the prepared pyridotriazolopyrimidines, several chemical descriptors were determined, including electronic, steric, and hydrophobic descriptors. These chemical descriptors were calculated in the polarizable continuum model (water as solvent) using density functional theory calculations at B3LYP/6-31+G(d,p). By employing simple linear regression (SLR) and multiple linear regression (MLR) analyses, the impact of the selected descriptors was assessed statistically. The obtained results clearly reveal that the cytotoxicity of pyridotriazolopyrimidines depends on their (i) basic skeleton and (ii) the type of the tested cell. Interestingly, SLR and MLR analyses show that the impact of the selected descriptors is strongly related to the tested cells and basic skeleton of the tested compounds. For instance, the cytotoxicity of subclasses 2a and 2c–2f against A459 shows strong correlation with ionization potential, hardness (η), and hydrophobicity (log P) with a correlation coefficient of 99.86% and a standard deviation of 0.53.
Highlights
Cancer is a complex ailment and remains a major health concern despite intensive efforts to elucidate its biology and develop more efficacious antitumor agents
The percentages of cell viability at 200 μg/mL are presented in Table 2 as the cytotoxicity parameter of the tested pyridotriazolopyrimidines
A considerable cytotoxicity was demonstrated by compounds 1a, 1b, 2a, 2c, 2e, 2d, 2f, 2i, 2m, 4, 5a, 5b, and 6c against A549
Summary
Cancer is a complex ailment and remains a major health concern despite intensive efforts to elucidate its biology and develop more efficacious antitumor agents. 1,2,4-triazoles are associated with various pharmacological activities, and a large number of predominant triazole drugs have been successfully developed and prevalently used in the treatment of various microbial infections such as fluconazole, posaconazole, and itraconazole (antifungal). Combining these three structure features in one molecule (pyridotriazolopyrimidine) has showed significant pharmacological efficiency as fungicidal, herbicidal, antidiabetic, and antioxidant agents [6,7,8,9,10,11]. Density functional theory (DFT) methods along with statistical analyses is employed to rationalize and confirm the relationship between the cytotoxicity and their correlated structures. We employed the polarizable continuum model (PCM) at the B3LYP/6-31+G(d,p) level of theory to calculate the electronic and steric molecular descriptors of the target pyridotriazolopyrimidines and utilized simple linear regression (SLR) and multiple linear regression (MLR) analyses to determine the correlation between the cytotoxicity of pyridotriazolopyrimidines and the calculated descriptors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
