368447-44-3Relevant academic research and scientific papers
Design, synthesis and screening of 4,6-diaryl pyridine and pyrimidine derivatives as potential cytotoxic molecules
Elhameid, Mohammed K. Abd,Ryad, Noha,My, Al-Shorbagy,Mohammed, Manal R.,Ismail, Mohammed M.,El Meligie, Salwa
, p. 939 - 952 (2018)
A new series of pyridine and pyrimidine derivatives is designed and synthesized as potential antitumor molecules. The tested compounds show promising in vitro cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14, 15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity 5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21 exhibit potent cell growth inhibition, cell cycle arrest at G2/M phase and proapoptotic inducing activities. The percentage inhibition assay of β-tubulin polymerization on HL-60 cells shows that the antitumor activity of the tested compounds appears to correlate well with its ability to inhibit β-tubulin polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA) measurement for compound 21 shows apoptotic inducing activities through significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel to down regulation of the level of survivin proteins.
Bu4NHSO4-Catalyzed Direct N-Allylation of Pyrazole and its Derivatives with Allylic Alcohols in Water: A Metal-Free, Recyclable and Sustainable System
Zhuang, Hongfeng,Lu, Nan,Ji, Na,Han, Feng,Miao, Chengxia
supporting information, p. 5461 - 5472 (2021/09/29)
Allylic amines are valuable and functional building blocks. Direct N-allylation of pyrazole and its derivatives as an atom economic strategy to provide allylic amines has been achieved only using commercial Bu4NHSO4 as the metal-free catalyst and water as the solvent without any additives. 11–93% isolated yields were obtained for the N-allylation of pyrazole and its derivatives with allylic alcohols. Bu4NHSO4 could be reused for six times by simple extraction nearly without loss of catalytic activity and was also suitable for a gram-scale production. The reaction of allylic ether and pyrazole did not occur to give the desired product indicated that allylic ether was not the active intermediate in the pathway. Density functional theory (DFT) calculations reveal that there are hydrogen bonding effects among substrates, solvent and catalyst, especially the one formed between allylic alcohol and H2O. Control experiments in different protic solvents further demonstrate the intermolecular hydrogen bonding of allylic alcohol and water. (Figure presented.).
Fluorinated benzylidene indanone exhibits antiproliferative activity through modulation of microtubule dynamics and antiangiogenic activity
Chanda, Debabrata,Fatima, Eram,Fatima, Kaneez,Khan, Feroz,Luqman, Suaib,Negi, Arvind S.,Shanker, Karuna,Shukla, Aparna,Singh, Aastha,Singh, Arjun,Srivastava, Ankita
, (2020/08/24)
The application of fluorine in drug design has been understood significantly by the medicinal chemists in recent years. Modulation of tubulin-microtubule dynamics is one of the most effective targets for cancer chemotherapeutics. A logically designed and identified lead compound, fluorinated benzylidene indanone 1 has been extensively evaluated for cancer pharmacology. It occupied colchicine binding pocket acting as microtubule destabilizer and induced a G2/M phase arrest in MCF-7 cells. Compound 1 exerted an antiangiogenic effect in MCF-7 cells by down-regulating Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-α (HIF-α). In in-vivo efficacy in C3H/Jax mice mammary carcinoma model, benzylidene indanone 1 reduced tumour volumes by 48.2%. Further in acute oral toxicity studies compound 1 was well tolerated and safe up to 1000 mg/kg dose in Swiss albino mice. The fluorinated benzylidene indanone 1, a new chemical entity (NCE) can further be optimized for better efficacy against breast adenocarcinoma.1
A class of novel tubulin polymerization inhibitors exert effective anti-tumor activity via mitotic catastrophe
Zhang, Ya-Liang,Li, Bo-Yan,Yang, Rong,Xia, Lin-Ying,Fan, A-Li,Chu, Yi-Chun,Wang, Lin-Jian,Wang, Zhong-Chang,Jiang, Ai-Qin,Zhu, Hai-Liang
, p. 896 - 910 (2019/01/04)
In current work, a class of novel 4,5-dihydro-1H-pyrazole-1-carboxylate derivatives (E01-E28) were designed, synthesized and evaluated. Among them, the most potent compound E24 exhibited comparable activity against a panel of cancer cells (GI50
3-Arylindanones and related compounds as antiproliferative agents against colorectal cancer
Srivastava, Ankita,Ravi, Kusumoori,Fatima, Kaneez,Maheshwari, Mayank,Ashraf, Raghib,Hasanain, Mohammad,Yadav, Pankaj,Iqbal, Hina,Kumar, Yogesh,Luqman, Suaib,Chanda, Debabrata,Khan, Feroz,Shanker, Karuna,Sarkar, Jayanta,Negi, Arvind Singh
, p. 1694 - 1705 (2019/07/16)
Diverse benzylidene indanones and their derivatives were synthesized as anticancer agents. Two of the analogues, that is 7 and 22, exhibited significant antiproliferative activity against several human cancer cell lines. Both the compounds possessed antimitotic activity and induced apoptosis in DLD1 colorectal adenocarcinoma cells through activation of caspase pathways. In cell cycle analysis, both the compounds induced predominantly G2/M phase arrest in DLD1 cells. Molecular docking studies revealed that compound 7 occupies colchicine binding pocket of β-tubulin. Both the compounds were safe in acute oral toxicity in rodents. Both the compounds are further being optimized for better efficacy.
Bi(OTf)3 catalyzed disproportionation reaction of cinnamyl alcohols
Chan, Chieh-Kai,Tsai, Yu-Lin,Chang, Meng-Yang
, p. 3368 - 3376 (2017/05/22)
Bi(OTf)3 catalyzed disproportionation reaction of cinnamyl alcohols provides chalcones and benzyl styrenes. The use of various metal triflates is investigated herein for facile and efficient redox transformation. A plausible mechanism has been proposed.
2-BENZYL-INDANONE COMPOUNDS AS ANTICANCER AGENT AND A PROCESS FOR PREPARATION THEREOF
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, (2017/02/09)
The anticancer activity of gallic acid compounds has been invented, in order to obtain new potent and cost effective molecule using in vitro cytotoxicity assay. The invention particularly relates to the gallic acid based new molecules i.e. 2-benzyl indanones represented by structure 1, possessing anticancer activity against human cancer cell lines. The compound also exhibited tubulin polymerisation inhibition. 2-(3',4'-methylenedioxybenzyl)-3-(3",4",5"-trimethoxyphenyl)-indanone- 1 (2), possessing molecular formulae as C29H30O9 was synthesized from gallic acid, exhibits potent in-vivo anticancer activity. Compound 2 was evaluated for acute oral activity in Swiss albino mice and it was found to be well tolerated by the experimental animals up to 300mg/kg body weight. (Formula 1, Formula 2).
Anticancer activity of gallic acid template-based benzylidene indanone derivative as microtubule destabilizer
Singh, Aastha,Fatima, Kaneez,Srivastava, Ankita,Khwaja, Sadiya,Priya, Dev,Singh, Arjun,Mahajan, Girish,Alam, Sarfaraz,Saxena, Ajit K.,Mondhe,Luqman, Suaib,Chanda, Debabrata,Khan, Feroz,Negi, Arvind S.
, p. 625 - 634 (2016/10/25)
Benzylidene indanones have been designed and synthesized from gallic acid, a plant phenolic acid as possible anticancer agent. The best analogue of the series, that is, 3-(3′,4′,5′-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4?-nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC50=3–10?μm) against several human cancer cell lines through microtubule destabilization (IC50=1.54?μm) after occupying colchicine-binding site of β-tubulin. In cell cycle analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite carcinoma in Swiss albino mice at 30?mg/kg dose. In acute oral toxicity experiment, it was tolerable up to 300?mg/kg doses in Swiss albino mice. The lead compound 8 needs to be optimized for better activity.
Synthesis of new N1-substituted-5-aryl-3-(3,4,5-trimethoxyphenyl)-2-pyrazoline derivatives as antitumor agents targeting the colchicine site on tubulin
Elmeligie, Salwa,Khalil, Nadia Abdalla,Ahmed, Eman Mohamed,Emam, Soha Hussein,Zaitone, Sawsan Abo-Bakr
, p. 1611 - 1622 (2016/10/09)
A series of pyrazoline derivatives 2a-e, 3a-e and 4a-e structurally related to combretastatin A4 (CA-4) were synthesized and characterized by spectroscopic means and elemental analyses. In these compounds, the cis double bond of CA-4 was replaced with the pyrazoline ring aiming to enhance the cytotoxic effects displayed by CA-4 and to prevent the cis/trans isomerization that is associated with inactivation of CA-4. The cytotoxic activity of all new compounds was investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by the most active compounds 3d, 4a and e was evaluated. The cytotoxicity of 4e was correlated with induction of apoptosis and caspase-3 activation in vitro thus indicating the apoptotic pathway of anticancer effect of these compounds. Furthermore, in vivo evaluation of the synthesized compounds was carried out against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. Compounds 2c, 3a and e showed significant reduction in tumor weight, and about 2-4 fold increase in caspase-3 expression.
Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents
Pathak, Vinay,Maurya, Hardesh K.,Sharma, Sandeep,Srivastava, Kishore K.,Gupta, Atul
supporting information, p. 2892 - 2896 (2014/06/10)
Various substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2- (heteroaryl)pyrimidine (6) and 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl) ethanone (7) derivatives were synthesized in good yields using simple methodology. The synthesized compounds (4-7)
