Pyrimidines-Based Heterocyclic Compounds: Synthesis, Cytoxicity Evaluation and Molecular Docking

Abstract

A variety of structurally different pyrimidines were synthesized. Elemental analysis, FT-IR, 1H NMR, and 13C NMR spectroscopy were used to confirm the chemical structures of all prepared compounds. The synthesized pyrimidines were screened against the growth of five human cancer cell lines (prostate carcinoma PC3, liver carcinoma HepG-2, human colon cancer HCT-116, human breast cancer MCF-7, human lung cancer A-549), and normal human lung fibroblasts (MRC-5) using MTT assay. Most of the screened pyrimidines have anti-proliferative activity on the growth of the PC3 cell line. Compounds 3b and 3d were more potent than the reference vinblastine sulfate (~2 to 3 × fold) and they can be considered promising leads for treating prostate cancer disease. Moreover, the screened compounds 3b, 3f, 3g, 3h, and 5 were assessed according to the values of their selectivity index (SI) and were found to be more selective and safer than vinblastine sulfate. Furthermore, using in silico computational tools, the physicochemical properties of all pyrimidine ligands were assessed, and the synthesized compounds fall within the criteria of RO5, thus having the potential to be orally bioavailable.

Synthesis of New Liquid-Crystalline Compounds Based on Terminal Benzyloxy Group: Characterization, DFT and Mesomorphic Properties

“…Furthermore, absolute electronegativity, χ, chemical potentials, µ, absolute hardness, η, absolute softness, σ, global electrophilicity, ω, global softness, S and additional electronic charge, ∆N max , have been calculated from the HOMO and LUMO energies (Table 3) to give indications about the reactivity and stability of the molecules studied [48,49].…”

Design, synthesis, in-silico studies and apoptotic activity of novel amide enriched 2-(1H)- quinazolinone derivatives

“…The quinazoline moiety serves as a fundamental structural unit in various physiologically active chemicals and medicinal molecules [ 18 ]. Quinazoline and quinazolinone derivatives have been attracted by biologists and medicinal chemists due to their diverse pharmacological activities [ 19 , 20 ], including anticancer [ [21] , [22] , [23] , [24] ], antitubercular [ [25] , [26] , [27] ], antimalarial [ 28 ], anti-inflammatory [ 29 , 30 ], antimicrobial [ 31 ], anticonvulsant [ 32 ], antihypertensive [ 33 , 34 ], antidiabetic [ 35 ], anti-HIV [ 36 ], antitumor [ [37] , [38] , [39] ], antioxidant [ 40 ], antiviral [ 41 ], kinase inhibitory [ 42 ], sedative-hypnotic, antihistaminic and many other uses [ 43 ]. Quinazoline and its derivatives are promising cancer chemotherapeutic agents for treating solid tumors [ [44] , [45] , [46] , [47] , [48] , [49] , [50] ].…”

Functionalization Strategies for Electropolishing Process of Carbon Steel Using Novel Quinazoline-4-one Derivatives: Synthesis, Spectroscopic Characterization, and DFT Studies

“…Further factors that command the inhibition process have been reported, including chain length, molecule size, the ability to cross-link, and molecule solubility. 6 Quinazoline-4(3H)-ones and their derivatives are a manysided heterocyclic composition that has garnered great interest due to their wide range of biological activities, including anticancer, 13 antitubercular, 14 antimicrobial, 15 antifungal, 16,17 anti-inflammatory, 18 anti-HIV, 19,20 analgesic, 21 anticonvulsant, 22 antitumor, 23,24 antihypertensive, 25 and antidiabetic activities. 26 Quinazoline becomes more reactive due to the tautomeric effect, enabling a wide range of activities; its ring is stable for oxidation, reduction, and hydrolysis processes.…”

“…In recent years, these heterocyclic compounds, which have significant biological activity, were effective corrosion inhibitors in an acidic medium . Since nitrogen atoms with a free pair of electrons operate as possible sites for bonding with metals, Quinazoline compounds have been the subject of extensive research − as inhibitors for improving corrosion resistance.…”