607-68-1Relevant articles and documents
Synthesis, characterization, crystal structure and cytotoxicity of 2,4-bis(selenomethyl)quinazoline
Plano, Daniel,Ibanez, Elena,Palop, Juan Antonio,Sanmartin, Carmen
, p. 1233 - 1240 (2011)
Organoselenium compounds have already been reported to be good anticarcinogenic candidates. A new selenoquinazoline derivative, 2,4-bis(selenomethyl)quinazoline (compound 1), has been synthesized, spectroscopically characterized and its crystal structure has been studied. An intermolecular coupling between C2 and H′ 5 in the Heteronuclear Multiple Bond Correlation (HMBC) experiment has been observed. Assuming that the headto- tail overlap of parallel molecules (as identified by X-ray diffraction) remains in solution to give bimolecular entities, the p-p interaction enables heteronuclear coupling between the former atoms with a three-bond distance [C2...(φ-φ)..C′ 5-H′ 5]. The crystal structure of compound 1 has been solved by X-ray diffraction. It crystallizes in triclinic system, space group P-1. Unit cell parameters are a = 7.4969(7) A , b = 8.7008(8) A , c = 10.1666(9) A , α = 110.215(2)-, β = 90.354(2)-, c = 115.017(1)-. Linear chains in crystals of compound 1 are generated by C-H...Se and Se..Se bonds between molecules. Furthermore, head-to-tail overlap of parallel molecules, in which p-p interactions can occur, is observed. Compound 1 exhibited a cytotoxic effect in all of the evaluated tumoral cell lines and showed a higher cytotoxic effect in colon and breast cancer cell lines than etoposide, which was used as a reference compound.
Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives
Cen, Shan,Wang, Juxian,Wang, Minghua,Wang, Yucheng,Wang, Yujia,Zhang, Guoning,Zhu, Mei
, (2020)
Four 2,4-disubstituted quinazoline series containing various amide moieties were designed and synthesized as new anti-influenza A virus agents using the strategies of bio-isosterism and scaffold hopping. Many of them exhibit potent in vitro anti-influenza A virus activity and low cytotoxicity (CC50: >100 μM). Particularly, compounds 10a5 and 17a show better activity (IC50: 3.70–4.19 μM) and higher selective index (SI: >27.03, >23.87, respectively) against influenza A/WSN/33 virus (H1N1), opening a new direction for quinazoline derivatives in anti-influenza A virus field.
Synthesis and antimicrobial activity of bis(azolyl)quinazoline-2,4-diamines
Rekha, Tamatam,Durgamma, Suram,Padmaja, Adivireddy,Padmavathi, Venkatapuram
, p. 1781 - 1792 (2017)
Abstract: Some new bis(azolylamino)- and bis(azolylmethylamino)quinazolines were prepared from 2,4-dichloroquinazoline and azolyl amines under ultrasonication and tested for their antimicrobial activity. The chloro-, bromo-, and nitro-substituted bis(thia
[1,2,4]Triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4′,3′-c]quinazoline derived DNA intercalators: Design, synthesis, in silico ADMET profile, molecular docking and anti-proliferative evaluation studies
El-Adl, Khaled,Ibrahim, Mohamed-Kamal,Alesawy, Mohammed S.I.,Eissa, Ibrahim H.
, (2021)
In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4′,3′-c]quinazoline derivatives have been designed, synthesized and evaluated against HepG2 and HCT-116. The molecular design was performed to investigate the binding mode of the proposed compounds with DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling studies. HCT-116 was found to be more sensitive cell lines to the influence of the new derivatives. In particular, compounds 16, 18, 11 and 5 were found to be the most potent derivatives with IC50 = 3.61, 6.72, 7.16 and 5.18 μM respectively against HepG2 cell line. Also, compounds 16, 18, 11 and 5 displayed IC50 = 2.85, 3.82, 4.97 and 6.40 μM respectively against HCT-116 cell line. These derivatives displayed higher activities than doxorubicin, (IC50 = 7.94 and 8.07 μM respectively) against the two HepG2 and HCT-116 cell lines. The most active anti-proliferative derivatives 5, 6, 10, 11, 13, 16, 18, 19 and 20 were further evaluated for their DNA-binding affinity which revealed the ability of these compounds to intercalate DNA. The tested compounds displayed very strong to moderate DNA-binding affinities. Compounds 16 and 18 potently intercalate DNA at IC50 values of 26.03 and 28.37 μM respectively which were lower than IC50 of Doxorubicin (IC50 = 31.27). This finding indicated that these derivatives exhibited higher DNA binding activities than Doxorubicin. Also, compounds 11 and 5 displayed very strong DNA binding at IC50 = 30.84 and 33.56 μM respectively, which were nearly equipotent to that of doxorubicin. Moreover, most of our derivatives exhibited good ADMET profile.
Design, synthesis and evaluation of anti-proliferative activity of 2-aryl-4-aminoquinazoline derivatives as EGFR inhibitors
Zhou, Zhihui,He, Jie,Yang, Feiyi,Pan, Qingshan,Yang, Zunhua,Zheng, Pengwu,Xu, Shan,Zhu, Wufu
, (2021/04/15)
A class of 2-aryl-4-aminoquinazoline derivatives (7a-7j, 8a-8h, 9a-9h and 10a-10k) were designed, synthesized and evaluated as EGFR inhibitors. The anti-proliferative activity of compounds in vitro showed that compound 9e was considered to be a promising derivative. Compared with the lead compound Angew2017-7634-1, 9e exhibited excellent inhibitory activity against A549, NCI-H460 and H1975 cell lines, with IC50 values of 14.33 ± 1.16 μM, 17.81 ± 1.25 μM and 13.41 ± 1.14 μM, respectively. Moreover, 9e could effectively inhibit against Ba/F3-EGFRDel19/T790M/C797S cell lines. In the kinase experiment, the most promising compound 9e exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M, with an IC50 value of 0.74 μM. Further activity studies showed that 9e could not only induce remarkable cell-apoptosis of A549, but also block A549 cell lines in S-phase in a concentration-dependent manner. Furthermore, molecular docking study revealed the binding mode of 9e. All in all, we analyzed the structure–activity relationship of the target compounds, and explored their mechanism of action.
1,2,4-Triazolo[4,3-c]quinazolines: a bioisosterism-guided approach towards the development of novel PCAF inhibitors with potential anticancer activity
El-Shershaby, Mohamed H.,Ghiaty, Adel,Bayoumi, Ashraf H.,Ahmed, Hany E. A.,El-Zoghbi, Mona S.,El-Adl, Khaled,Abulkhair, Hamada S.
, p. 11136 - 11152 (2021/07/06)
Targeting PCAF with small inhibitor molecules has emerged as a potential therapeutic strategy for the treatment of cancer. Recently, L-45 was identified as a potent triazolophthalazine inhibitor of the PCAF bromodomain. Here, we report the bioisosteric modification of the triazolophthalazine ring system of L-45 to its bioisosteric triazoloquinazoline while maintaining other essential structural fragments for effective binding with the binding site of PCAF. Consequently, a set of sixteen triazoloquinazoline derivatives were designed, synthesized, and investigated for their anticancer activity against four human cancer cell lines. Five derivatives demonstrated comparable cytotoxic activity with that of doxorubicin as a reference anticancer drug. Among them, compound23showed the most potent activity with IC50values of 6.12, 4.08, 7.17, and 6.42 μM against HePG2, MCF-7, PC3, and HCT-116, respectively. Also, compound21exhibited comparable cytotoxic effects with that of doxorubicin against the selected cancer cell lines with IC50values in the range of 7.41-9.58 μM. Molecular docking and pharmacokinetic studies were additionally performed to rationalize the binding affinities of the newly designed triazoloquinazolines toward the active site of histone acetyltransferase PCAF and to evaluate the druggability of new compounds. The results of these studies suggested that PCAF binding could be the mechanism of action of these derivatives.
