607-68-1Relevant academic research and scientific papers
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.
From triazolophthalazines to triazoloquinazolines: A bioisosterism-guided approach toward the identification of novel PCAF inhibitors with potential anticancer activity
El-Shershaby, Mohamed H.,Ghiaty, Adel,Bayoumi, Ashraf H.,Al-Karmalawy, Ahmed A.,Husseiny, Ebtehal M.,El-Zoghbi, Mona S.,Abulkhair, Hamada S.
, (2021)
Inhibition of PCAF bromodomain has been validated as a promising strategy for the treatment of cancer. In this study, we report the bioisosteric modification of the first reported potent PCAF bromodomain inhibitor, L-45 to its triazoloquinazoline bioisosteres. Accordingly, three new series of triazoloquinazoline derivatives were designed, synthesized, and assessed for their anticancer activity against a panel of four human cancer cells. Three derivatives demonstrated comparable cytotoxic activity with the reference drug doxorubicin. Among them, compound 22 showed the most potent activity with IC50 values of 15.07, 9.86, 5.75, and 10.79 μM against Hep-G2, MCF-7, PC3, and HCT-116 respectively. Also, compound 24 exhibited remarkable cytotoxicity effects against the selected cancer cell lines with IC50 values of 20.49, 12.56, 17.18, and 11.50 μM. Compounds 22 and 25 were the most potent PCAF inhibitors (IC50, 2.88 and 3.19 μM, respectively) compared with bromosporine (IC50, 2.10 μM). Follow up apoptosis induction and cell cycle analysis studies revealed that the bioisostere 22 could induce apoptotic cell death and arrest the cell cycle of PC3 at the G2/M phase. The in silico molecular docking studies were additionally performed to rationalize the PCAF inhibitory effects of new triazoloquinazoline bioisosteres.
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.
Design and discovery of new 1,2,4-triazolo[4,3-c]quinazolines as potential DNA intercalators and topoisomerase II inhibitors
Alesawy, Mohamed S.,Al-Karmalawy, Ahmed A.,Elkaeed, Eslam B.,Alswah, Mohamed,Belal, Ahmed,Taghour, Mohammed S.,Eissa, Ibrahim H.
, (2021)
A new series of 1,2,4-triazolo[4,3-c]quinazoline derivatives was designed and synthesized as Topo II inhibitors and DNA intercalators. The cytotoxic effect of the new members was evaluated in vitro against a group of cancer cell lines including HCT-116, HepG-2, and MCF-7. Compounds 14c, 14d, 14e, 14e, 15b, 18b, 18c, and 19b exhibited the highest activities with IC50 values ranging from 5.22 to 24.24 μM. Furthermore, Topo II inhibitory activities and DNA intercalating affinities of the most promising candidates were evaluated as a possible mechanism for the antiproliferative effect. The results of the Topo II inhibition and DNA binding tests were coherent with that of in vitro cytotoxicity. Additionally, the most promising compound 18c was analyzed in HepG-2 cells for its apoptotic effect and cell cycle arrest. It was found that 18c can induce apoptosis and arrest the cell cycle at the G2–M phase. Finally, molecular docking studies were carried out for the designed compounds against the crystal structure of the DNA?Topo II complex as a potential target to explore their binding modes. On the basis of these studies, it was hypothesized that the DNA binding and/or Topo II inhibition would participate in the noted cytotoxicity of the synthesized compounds.
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
Discovery of new coumarin substituted quinazolines as potential bioactive agents
Patel, Amit B.,Raval, Rinku M.
, p. 2163 - 2175 (2016)
In view of the biological importance of some important pharmacophores such as quinazoline, coumarin, and benzothiazole, we frame these moieties in a single molecular scaffold to be screened in vitro for their antimicrobial activity. The newly synthesized analogs have been examined for their in vitro biological efficacy against two Gram-positive bacteria, three Gram-negative bacteria, two fungi, and for antimycobacterial activity against M. tuberculosis H37Rv. The bioassay results revealed that the majority of final analogs exhibited potential bio efficacies with the remarkable level of MICs comparable to control drugs. The new synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR, and MS analysis.
[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, in silico ADMET, docking, and antiproliferative evaluations of [1,2,4]triazolo[4,3-c]quinazolines as classical DNA intercalators
Alesawy, Mohamed S.,Eissa, Ibrahim H.,El-Adl, Khaled,Ibrahim, Mohamed-Kamal
, (2022/01/13)
Eleven novel [1,2,4]triazolo[4,3-c]quinazolines were designed, synthesized, and evaluated against HepG2 and HCT-116 cells. The molecular design was performed to investigate the binding mode of the proposed compounds with the DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling. HCT-116 was found to be the most sensitive cell line to the influence of the new derivatives. In particular, compounds 6f and 6e were found to be the most potent derivatives over all the tested compounds against the two HepG2 and HCT116 cancer cell lines, with IC50 = 23.44 ± 2.9, 12.63 ± 1.2, and 25.80 ± 2.1, and 14.32 ± 1.5 μM, respectively. Although compounds 6f and 6e displayed less activity than doxorubicin (IC50 = 7.94 ± 0.6 and 8.07 ± 0.8 μM, respectively), both could be useful as a template for future design, optimization, and investigation to produce more potent anticancer analogs. The most active derivatives 6a, 6c, 6e, and 6f were evaluated for their DNA-binding activities. Compound 6f displayed the highest binding affinity. This compound potently intercalates DNA at a decreased IC50 value (54.08 μM). Compounds 6a, 6c, and 6e exhibited good DNA-binding affinities, with IC50 values of 79.35, 84.08, and 59.35 μM, respectively. Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiles were calculated for the four most active compounds in comparison to doxorubicin as a reference drug. Our derivatives 6a, 6c, 6e, and 6f displayed very good in-silico-predicted ADMET profiles. Doxorubicin violates three of Lipinski's rules, our derivatives 6a, 6c, 6e, and 6f do not violate any rule.
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.
Discovery of quinazolinyl-containing benzamides derivatives as novel HDAC1 inhibitors with in vitro and in vivo antitumor activities
Zhang, Zixue,Zhang, Qingwei,Zhang, Hao,Jiao, Minru,Guo, Zheng,Peng, Xinyan,Fu, Lei,Li, Jianqi
, (2021/10/16)
A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo.
