Amrutha Arjunan1, Sankar Pajaniradje2, Arul Prakash Francis1, Srividya Subramanian1, Sathyapriya Chandramohan1, D Parthasarathi3, Ayyiliath M Sajith4, M Syed Ali Padusha3, P P Mathur1, Rukkumani Rajagopalan5. 1. Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, Puducherry, 605 014, India. 2. Centre for Nanoscience and Technology, Anna University, Chennai, Tamil Nadu, 600025, India. 3. Postgraduate and Research Department of Chemistry, Jamal Mohamed College, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620 020, India. 4. Postgraduate and Research Department of Chemistry, Kasaragod Government College, Kannur University, Kasaragod, Kerala, 671123, India. 5. Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, Puducherry, 605 014, India. ruks2k2@gmail.com.
Abstract
PURPOSE: Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazo-benzamides are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel imidazo-benzamide derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. METHODS: The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. RESULTS: TBUEIB inhibited fifty precent A549 cells at a dose of 106 μM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. CONCLUSION: The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound.
PURPOSE: Lung cancer is the most commonly diagnosed and leading cause of cancer death worldwide. Imidazo-benzamides are considered to be good anti-cancer agents. The present study was aimed to investigate the cytotoxicity of a novel imidazo-benzamide derivative N-(2-(3-(tert-butyl)ureido)ethyl)-4-(1H-imidazol-1-yl)benzamide (TBUEIB) in lung cancer cell line A549. METHODS: The antiproliferative activity of TBUEIB was investigated using MTT, LDH and trypan blue assay. The apoptotic potential was investigated using various staining techniques and further confirmed by DNA fragmentation assay and western blotting. RESULTS: TBUEIB inhibited fifty precent A549 cells at a dose of 106 μM. The novel compound was found to exert a modulatory effect on apoptotic marker caspase-3 as well as epigenetic regulatory proteins like DNA Methyltransferase 1 (DNMT1). In silico studies with the compound and other epigenetic proteins such as Histone deacetylase (HDAC) and ubiquitin-like with PHD (plant homeodomain) and RING (Really Interesting New Gene) finger domains 1(UHRF1) showed good modulatory effects. CONCLUSION: The overall results obtained in the study conclude that the novel compound TBUEIB has potential anti-cancer activities, mainly by targeting the expression of DNMT1 enzyme, which may have re-activated the major tumor suppressor genes involved in the cell cycle, leading to the apoptosis of the cancer cells. The results also indicate that the compound has more than one target in the epigenetic pathway implying that the compound may be a potential multi-target compound.
Authors: Jianqing Lin; Michael C Haffner; Yonggang Zhang; Byron H Lee; W Nathaniel Brennen; Justin Britton; Sushant K Kachhap; Joong Sup Shim; Jun O Liu; William G Nelson; Srinivasan Yegnasubramanian; Michael A Carducci Journal: Prostate Date: 2010-08-31 Impact factor: 4.104
Authors: Brian D Larsen; Shravanti Rampalli; Leanne E Burns; Steve Brunette; F Jeffrey Dilworth; Lynn A Megeney Journal: Proc Natl Acad Sci U S A Date: 2010-02-16 Impact factor: 11.205
Authors: Mahmoud Alhosin; Ziad Omran; Mazin A Zamzami; Abdulrahman L Al-Malki; Hani Choudhry; Marc Mousli; Christian Bronner Journal: J Exp Clin Cancer Res Date: 2016-11-14