1565-90-8Relevant academic research and scientific papers
Pharmacophore hybridization approach to discover novel pyrazoline-based hydantoin analogs with anti-tumor efficacy
Upadhyay, Neha,Tilekar, Kalpana,Loiodice, Fulvio,Anisimova, Natalia Yu.,Spirina, Tatiana S.,Sokolova, Darina V.,Smirnova, Galina B.,Choe, Jun-yong,Meyer-Almes, Franz-Josef,Pokrovsky, Vadim S.,Lavecchia, Antonio,Ramaa
, (2020/12/21)
In search for new and safer anti-cancer agents, a structurally guided pharmacophore hybridization strategy of two privileged scaffolds, namely diaryl pyrazolines and imidazolidine-2,4-dione (hydantoin), was adopted resulting in a newfangled series of compounds (H1-H22). Herein, a bio-isosteric replacement of “pyrrolidine-2,5-dione” moiety of our recently reported antitumor hybrid incorporating diaryl pyrazoline and pyrrolidine-2,5-dione scaffolds with “imidazoline-2,4-dione” moiety has been incorporated. Complete biological studies revealed the most potent analog among all i.e. compound H13, which was at-least 10-fold more potent compared to the corresponding pyrrolidine-2,5-dione, in colon and breast cancer cells. In-vitro studies showed activation of caspases, arrest of G0/G1 phase of cell cycle, decrease in the expression of anti-apoptotic protein (Bcl-2) and increased DNA damage. In-vivo assay on HT-29 (human colorectal adenocarcinoma) animal xenograft model unveiled the significant anti-tumor efficacy along with oral bioavailability with maximum TGI 36% (i.p.) and 44% (per os) at 50 mg/kg dose. These findings confirm the suitability of hybridized pyrazoline and imidazolidine-2,4-dione analog H13 for its anti-cancer potential and starting-point for the development of more efficacious analogs.
Design, synthesis and insecticidal activity of novel semicarbazones and thiosemicarbazones derived from chalcone
Cheng, Wei,Xiao, Tingting,Qian, Weifeng,Lu, Tong,Zhang, Tingting,Tang, Xiaorong
, p. 3801 - 3809 (2020/03/23)
Thirty semicarbazone and thiosemicarbazone derivatives (2a–w and 4a–g) from chalcones containing furan and thiophene ring were designed and synthesized. They were characterized by IR, 1H NMR, 13C NMR and HRMS. The crystal structure o
2,4,6-trisubstituted pyridine compound and application thereof in pesticide
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Paragraph 0064; 0066, (2021/06/13)
The invention relates to a 2,4,6-trisubstituted pyridine compound and application thereof in pesticides, and belongs to the technical field of pesticides. The structural formula of the 2,4,6-trisubstituted pyridine compound is as shown in formula (I), in
Multi-target weapons: diaryl-pyrazoline thiazolidinediones simultaneously targeting VEGFR-2 and HDAC cancer hallmarks
C S, Ramaa,Kumar, Alan P.,Meyer-Almes, Franz-Josef,Safuan, Sabreena,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha
, p. 1540 - 1554 (2021/10/26)
In anticancer drug discovery, multi-targeting compounds have been beneficial due to their advantages over single-targeting compounds. For instance, VEGFR-2 has a crucial role in angiogenesis and cancer management, whereas HDACs are well-known regulators o
Double-edged Swords: Diaryl pyrazoline thiazolidinediones synchronously targeting cancer epigenetics and angiogenesis
Kumar, Alan P.,Meyer-Almes, Franz-Josef,Ramaa, C. S.,Safuan, Sabreena,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha
, (2021/09/22)
In the present study, two novel series of compounds incorporating naphthyl and pyridyl linker were synthesized and biological assays revealed 5-((6-(2-(5-(2-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethoxy) naphthalene-2-yl)methylene)thiazolidine-2,4-dione (14b) as the most potent dual inhibitors of vascular endothelial growth factors receptor-2 (VEGFR-2) and histone deacetylase 4 (HDAC4). Compounds 13b, 14b, 17f, and 21f were found to stabilize HDAC4; where, pyridyl linker swords were endowed with higher stabilization effects than naphthyl linker. Also, 13b and 14b showed best inhibitory activity on VEGFR-2 as compared to others. Compound 14b was most potent as evident by in-vitro and in-vivo biological assessments. It displayed anti-angiogenic potential by inhibiting endothelial cell proliferation, migration, tube formation and also suppressed new capillary formation in the growing chick chorioallantoic membranes (CAMs). It showed selectivity and potency towards HDAC4 as compared to other HDAC isoforms. Compound 14b (25 mg/kg, i.p.) also indicated exceptional antitumor efficacy on in-vivo animal xenograft model of human colorectal adenocarcinoma (HT-29). The mechanism of action of 14b was also confirmed by western blot.
Synthesis, biological activities, and docking study of novel chalcone-pleuromutilin derivatives
Xie, Chuan,Zhang, Siyu,Zhang, Wei,Wu, Chunxia,Yong, Can,Sun, Yuhao,Zeng, Zhengxing,Zhang, Qian,Huang, Zixin,Chen, Tian,Zhang, Yuanyuan
, p. 836 - 849 (2020/04/30)
The issue of antibiotic resistance is becoming progressively serious these days, and the feasible solution to address it is to develop and discover novel antibiotics. The diterpene natural pleuromutilin is a prominent candidate for its special mode of act
Synthesis and Biological Evaluation of Pyrazoline and Pyrrolidine-2,5-dione Hybrids as Potential Antitumor Agents
Anisimova, Natalia Y.,Choe, Jun-yong,Lavecchia, Antonio,Loiodice, Fulvio,Meyer-Almes, Franz-Josef,Pokrovsky, Vadim S.,S Ramaa, C.,Smirnova, Galina B.,Sokolova, Darina V.,Spirina, Tatiana S.,Tilekar, Kalpana,Upadhyay, Neha
, p. 1813 - 1825 (2020/09/07)
In search of novel and effective antitumor agents, pyrazoline-substituted pyrrolidine-2,5-dione hybrids were designed, synthesized and evaluated in silico, in vitro and in vivo for anticancer efficacy. All the compounds exhibited remarkable cytotoxic effects in MCF7 and HT29 cells. The excellent antiproliferative activity toward MCF7 (IC50=0.78±0.01 μM), HT29 (IC50=0.92±0.15 μM) and K562 (IC50=47.25±1.24 μM) cell lines, prompted us to further investigate the antitumor effects of the best compound S2 (1-(2-(3-(4-fluorophenyl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione). In cell-cycle analysis, S2 was found to disrupt the growth phases with increased cell population in G1/G0 phase and decreased cell population in G2/M phase. The excellent in vitro effects were also supported by inhibition of anti-apoptotic protein Bcl-2. In vivo tumor regression studies of S2 in HT29 xenograft nude mice, exhibited equivalent and promising tumor regression with maximum TGI, 66 % (i. p. route) and 60 % (oral route) at 50 mg kg?1 dose by both the routes, indicating oral bioavailability and antitumor efficacy. These findings advocate that hybridization of pyrazoline and pyrrolidine-2,5-dioes holds promise for the development of more potent and less toxic anticancer agents.
Facile one pot multicomponent synthesis of novel 4-(benzofuran-2-yl)-2-(3-(aryl/heteryl)-5-(aryl/heteryl)-4,5-dihydro-1H-pyrazol-1yl)thiazole derivatives
Arandkar, Varun,Vaarla, Krishnaiah,Vedula, Rajeswar Rao
, p. 1285 - 1290 (2018/05/30)
An efficient base catalyzed one pot multicomponent reaction of aryl/hetryl chalcones, thiosemicarbazide and 1-(benzofuran-2-yl)-2-bromoethan-1-one was developed to synthesize the novel 4-(benzofuran-2-yl)-2-(3-(aryl/heteryl)-5-(aryl/heteryl)-4,5-dihydro-1H-pyrazol-1yl)thiazole derivatives.
1-(2-furyl)-3-(4-substituted phenyl)propylene derivative as well as preparation method and application thereof
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Paragraph 0034; 0035, (2016/10/07)
The invention provides a 1-(2-furyl)-3-(4-substituted phenyl)propylene derivative as well as a preparation method and application thereof. The derivative has a structural formula (I) shown in the following description; in the structural formula (I), R is
3-(2-furyl)propenol derivative as well as preparation method and application thereof
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Paragraph 0032; 0033, (2016/10/09)
The invention provides a 3-(2-furyl)propenol derivative as well as a preparation method and application thereof. The derivative has a structural formula (I) shown in the following description; in the structural formula (I), R is a fluorine atom, a chlorin
