- Synthesis of 2-anilinopyridyl linked benzothiazole hydrazones as apoptosis inducing cytotoxic agents
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A series of 2-anilinopyridyl linked benzothiazole-hydrazone conjugates (5a-aa) were designed, synthesized and evaluated for their in vitro cytotoxic potency against a panel of cancer cell lines like mouse skin melanoma (B16F10), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), triple negative breast cancer (MDA-MB-231) and normal lung epithelial (L132) cell lines. Preliminary screening results revealed that some of these conjugates like 5i and 5l exhibited a significant antiproliferative effect against human breast cancer (MCF-7) with IC50 values of 1.03 and 1.69 μM respectively. Further, detailed biological studies of this promising conjugate (5i) were carried out on MCF-7 cells. The flow cytometric analysis revealed that this conjugate induces cell-cycle arrest in the G2/M phase in a dose dependent manner. Furthermore, in order to determine the effect of the conjugate on cell viability, various cell based assays such as clonogenic assay, ethidium bromide staining, Hoechst staining, detection of ROS generation and annexin V-FITC/PI assays were performed. In these studies, apoptotic features were clearly observed indicating that this conjugate inhibited cell proliferation by apoptosis.
- Sultana, Faria,Saifi, Mohd Aslam,Syed, Riyaz,Mani, Geeta Sai,Shaik, Siddiq Pasha,Osas, Egharevba God'Shelp,Godugu, Chandraiah,Shahjahan, Syeda,Kamal, Ahmed
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p. 7150 - 7161
(2019/05/17)
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- Design, synthesis and antiproliferative activity of the new conjugates of E7010 and resveratrol as tubulin polymerization inhibitors
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A new class of (E)-N-phenyl-3-styrylpyridin-2-amine conjugates were designed and synthesized on the basis of E7010 and resveratrol scaffolds. These conjugates were evaluated for their antiproliferative activity in four human cancer cell lines with GI50 values ranging from 2.1 μM to 20 μM. Two of the conjugates RSV-1 and RSV-11 were found to possess 13-fold higher GI50 values than resveratrol and 1 to 2 fold higher GI50 values than E7010 against the human cervical HepG2 cancer line. They displayed high potency and selectivity in a panel of NCI 60 human cancer cell lines. Based on the GI50 values against the panel of 60 NCI cancer cell lines and dock scores from the molecular modelling studies, we selected RSV-1 and RSV-11 for tubulin polymerization and mechanistic studies. Furthermore, RSV-1 and RSV-11 compounds inhibited the assembly of tubulin by strongly binding to the colchicine-binding site. The G2/M-phase is arrested in HepG2 cells as assessed by flow cytometry. Structure based studies, western blotting and immunofluorescence experiments demonstrated that RSV-1 and RSV-11 depolymerize microtubules in the HepG2 cell line, resulting in an accumulation of G2/M cells.
- Kamal, Ahmed,Ashraf,Basha, Shaik Thokhir,Ali Hussaini,Singh, Shamshair,Vishnuvardhan,Kiran, Boppana,Sridhar, Balasubramanian
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p. 1382 - 1394
(2016/02/03)
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- Synthesis of 2-anilinopyridine-arylpropenone conjugates as tubulin inhibitors and apoptotic inducers
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A series of new (Z)-3-(arylamino)-1-(2-(arylamino)pyridin-3-yl)prop-2-en-1-one conjugates 9a-p were synthesized and evaluated for their cytotoxic activity against some human cancer cell lines. Some of the treated compounds like 9a, 9g and 9j showed significant activity with IC50 values ranging from 0.51 to 1.29 μM. Flow cytometry results revealed that for A549 cells these compounds caused accumulation of cells in the G2/M phase. Interestingly, compound 9a demonstrated a considerable inhibitory effect on tubulin polymerization and showed significant inhibition of tubulin polymerization with an IC50 value of 1.34 μM, whereas nocodazole showed antitubulin activity with an IC50 value 2.64 μM. Further, Hoechst staining and activation of caspase-3 suggested that these conjugates induced cell death by apoptosis. Fluorescence based competitive colchicine binding assay and docking studies suggest that these conjugates 9a and 9g bind to the tubulin perfectly at the colchicine binding site.
- Kamal, Ahmed,Reddy, Vangala Santhosh,Vishnuvardhan,Kumar, G. Bharath,Shaik, Anver Basha,Chourasiya, Sumit S.,Reddy, M. Kashi,Sayeed, Ibrahim Bin,Adiyala, Praveen Reddy,Jain, Nishant
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p. 97367 - 97380
(2015/12/01)
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- Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers
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A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC 50 value of 4.01 μM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.
- Kamal, ?hmed,Ashraf, Md.,Vishnu Vardhan,Faazil, Shaikh,Nayak, V. Lakshma
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p. 147 - 151
(2014/01/17)
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- C-H cycloamination of N-aryl-2-aminopyridines and N-arylamidines catalyzed by an in situ generated hypervalent iodine(iii) reagent
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A metal-free synthesis of diversified pyrido[1,2-a]benzimidazoles and 1H-benzo[d]imidazoles from N-aryl-2-aminopyridines and N-arylamidines has been developed. The C-H cycloamination reaction was catalyzed by hypervalent iodine(iii) species generated in situ from iodobenzene (catalytic) and peracetic acid (stoichiometric). The reaction proceeded smoothly at ambient temperature to provide the corresponding N-heterocycles in good to excellent yields.
- He, Yimiao,Huang, Jinbo,Liang, Dongdong,Liu, Lanying,Zhu, Qiang
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supporting information
p. 7352 - 7354
(2013/09/23)
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- 2-ANILINO NICOTINYL LINKED 2-AMINO BENZOTHIAZOLE CONJUGATES AND PROCESS FOR THE PREPARATION THEREOF
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The present invention provides compounds of general formula A useful as potential anticancer agents against human cancer cell lines and apoptosis inducers. The present invention further provides a process for the preparation of 2-anilino nicotinyl linked 2-amino benzothiazole conjugates of general formula (A), wherein R1═H or CI; R2═H, OCH3 or F; R3═H, OCH3, F or CI; R4═H, OCH3 or F and X═OCH3, F or N02.
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Paragraph 0095
(2014/01/07)
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- 2-ANILINO NICOTINYL LINKED 2-AMINO BENZOTHIAZOLE CONJUGATES AND PROCESS FOR THE PREPARATION THEREOF
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The present invention provides compounds of general formula A useful as potential anticancer agents against human cancer cell lines and apoptosis inducers. The present invention further provides a process for the preparation of 2-anilino nicotinyl linked 2-amino benzothiazole conjugates of general formula (A), wherein R1 = H or CI; R2 = H, OCH3 or F; R3 = H, OCH3, F or CI; R4=H, OCH3 or F and X= OCH3, F or N02.
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Page/Page column 16-17
(2012/09/10)
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- 2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers
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A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and
- Kamal, Ahmed,Srikanth,Naseer Ahmed Khan,Ashraf, Md.,Kashi Reddy,Sultana, Farheen,Kaur, Tandeep,Chashoo, Gousia,Suri, Nitasha,Sehar, Irum,Wani, Zahoor A.,Saxena, Arpita,Sharma, Parduman R.,Bhushan, Shashi,Mondhe, Dilip M.,Saxena, Ajit K.
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experimental part
p. 7136 - 7150
(2012/01/02)
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- Synthesis of a new class of 2-anilino substituted nicotinyl arylsulfonylhydrazides as potential anticancer and antibacterial agents
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A series of N′-1-[2-anilino-3-pyridyl]carbonyl-1-benzenesulfonohydrazide derivatives (7a-i) was synthesized and five of them were selected by the National Cancer Institute (NCI) and evaluated for their in vitro anticancer activity. Three of the investigat
- Kamal, Ahmed,Khan, M. Naseer A.,Srinivasa Reddy,Rohini
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p. 1004 - 1013
(2007/10/03)
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- Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors
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A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC 50 values in the single digit nanomolar range. Binding experiments demonstrated that representative
- Ouyang, Xiaohu,Chen, Xiaoling,Piatnitski, Evgueni L.,Kiselyov, Alexander S.,He, Hai-Ying,Mao, Yunyu,Pattaropong, Vatee,Yu, Yang,Kim, Ki H.,Kincaid, John,Smith II, Leon,Wong, Wai C.,Lee, Sui Ping,Milligan, Daniel L.,Malikzay, Asra,Fleming, James,Gerlak, Jason,Deevi, Dhanvanthri,Doody, Jacqueline F.,Chiang, Hui-Hsien,Patel, Sheetal N.,Wang, Ying,Rolser, Robin L.,Kussie, Paul,Labelle, Marc,Tuma, M. Carolina
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p. 5154 - 5159
(2007/10/03)
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- Antiallergy Agents. 1. Substituted 1,8-Naphthyridin-2(1H)-ones as Inhibitors of SRS-A Release
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A novel class of antiallergy agents, the substituted 1,8-naphthyridin-2(1H)-ones, is described.The present compounds are orally active, potent inhibitors of allergic and nonallergic bronchospasm in animal models.Structure-activity studies of the lead compound in this sereis, 1-phenyl-3-n-butyl-4-hydroxynaphthyridin-2(1H)-one (11), identified three compounds of interest, 1-phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one (12), 1-(3'-chlorophenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one (87), and 1-(3'-methoxyphenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one (89).The mechanism of antiallergy activity may involve inhibition of the release of the sulfidopeptide leukotrienes. 1-Phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one, Sch 33303 (12), was selected for preclinical development as an antiallergy agent.
- Sherlock, Margaret H.,Kaminski, James J.,Tom, Wing C.,Lee, Joe F.,Wong, Shing-Chun,et al.
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p. 2108 - 2121
(2007/10/02)
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