1,2,3‐Triazole Tagged 3H‐Pyrano[2,3‐d]pyrimidine‐6‐carboxylate Derivatives: Synthesis, in Vitro Cytotoxicity, Molecular Docking and DNA Interaction Studies

Abstract

A series of novel ethyl 2,7-dimethyl-4-oxo-3-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-4,5-dihydro-3H-pyrano[2,3-d]pyrimidine-6-carboxylate derivatives 7a - 7m were efficiently synthesized employing click chemistry approach and evaluated for in vitro cytotoxic activity against four tumor cell lines: A549 (human lung adenocarcinoma cell line), HepG2 (human hematoma), MCF-7 (human breast adenocarcinoma), and SKOV3 (human ovarian carcinoma cell line). Among the compounds tested, the compounds 7a, 7b, 7f, 7l, and 7m have shown potential and selective activity against human lung adenocarcinoma cell line (A549) with IC ranging from 0.69 to 6.74 μm. Molecular docking studies revealed that the compounds 7a, 7b, 7f, 7l, and 7m are potent inhibitors of human DNA topoisomerase-II and also showed compliance with stranded parameters of drug likeness. The calculated binding constants, k , from UV/VIS absorptional binding studies of 7a and 7l with CT-DNA were 10.77 × 10 , 6.48 × 10 , respectively. Viscosity measurements revealed that the binding could be surface binding mainly due to groove binding. DNA cleavage study showed that 7a and 7l have the potential to cleave pBR322 plasmid DNA without any external agents.

Synthesis of quinazolindionyl amino acid and dipeptide derivatives as possible antitumour agents

“…The two hydrazides 3 and 6 were characterized by their higher melting points and lower Rf values relative to the parent ester derivatives. 1 H NMR spectra of the synthesized hydrazides 3 and 6 showed the characteristic signals of the hydrazide group as two singlet signals at 9.31 ppm and 9.12 ppm for the proton of NH and at 4.27 ppm and 4.17 ppm for the two protons of NH2 respectively. Also, 13 C NMR spectra displayed the disappearance of the two signals of the ethyl ester group at 62.0 ppm and 14.1 ppm and the signal of OCH3 carbon of the ester at 52.0 ppm which confirms the formation of the hydrazides.…”

“…Based upon the comparable activity of 3-nitrobenzylidene hydrazone derivative 8c with doxorubicin, it is necessary to extend this study to synthesize other hydrazones, bearing different substituents on the benzylidene nucleus. The azide method seemed to be suitable activation procedure for the formation of pure amino acid and dipeptide derivatives, not contaminated with the by-product urea derivatives, when carried out at 0 o C. 1 H and 13 C NMR data supported the occurrence of alkylation and Michael addition at nitrogen (N-1) and not oxygen atom.…”

“…The chemical structures of the ester derivatives 2 and 5 were assigned by elemental analysis, 1 H NMR and 13 C NMR spectra (see the experimental part). 1 H NMR spectrum of compound 2 showed a singlet signal at 4.90 ppm corresponding to the two protons of the acetate moiety NCH2CO and the 13 C NMR spectrum of this compound displayed a signal at 44.9 ppm attributable to the carbon of the same group.…”

“…The chemical structures of the ester derivatives 2 and 5 were assigned by elemental analysis, 1 H NMR and 13 C NMR spectra (see the experimental part). 1 H NMR spectrum of compound 2 showed a singlet signal at 4.90 ppm corresponding to the two protons of the acetate moiety NCH2CO and the 13 C NMR spectrum of this compound displayed a signal at 44.9 ppm attributable to the carbon of the same group. Moreover, the 1 H NMR spectrum of the propionyl derivative 5 showed the characteristic signals of the methyl propionate moiety as a triplet signal at 4.37 ppm for the two protons of the β-carbon of the propionate (NCH2), the two protons of the α-carbon (CH2CO) appeared as triplet signal at 2.79 ppm, and the 13 C NMR spectrum exhibited signal at 31.8 ppm attributable to the α-carbon of the propionate moiety.…”

“…According to the World Health Organization, it caused a quarter of all deaths in the developed world during the last decade. [1][2][3][4][5] Chemotherapy is a main method for the treatment of almost all types of cancer solely or with combination with another treatment approach. Despite much progress in the chemotherapy of cancer, there are several problems in cancer treatment by cytotoxic drugs that need to be solved such as the side effects arising from the indiscriminating action of the drugs on both cancerous and healthy tissues.…”