Synthesis and Characterization of a New Benzoindole Derivative with Apoptotic Activity Against Colon Cancer Cells.
Colorectal cancer is the third most common form of cancer in both men and women around the world. The chemistry and biological study of heterocyclic compounds have been an interesting area for a long time in pharmaceutical and medicinal chemistry.



A new synthetic compound, 2-(1,1-dimethyl-1H-benzo[e]indol-2-yl)-3-((2-hydroxyphenyl)amino) acrylaldehyde, abbreviated as DBID, was prepared through the reaction of 2-(diformylmethylidene)-1,1- dimethylbenzo[e]indole with 2-aminophenol. The chemical structure of the synthesized compound was characterized by 1H NMR, 13C NMR and APT-NMR spectroscopy and confirmed by elemental analysis (CHN). The compound was screened for the antiproliferation effect against colorectal cancer cell line, HCT 116 and its possible mechanism of action was elucidated. To determine the IC50 value, the MTT assay was used and its apoptosisinducing effect was investigated.



DBID inhibited the proliferation of HCT 116 cells with an IC50 of 9.32 µg/ml and significantly increased the levels of caspase -8, -9 and -3/7 in the treated cells compared to untreated cells. Apoptosis features in HCT 116 cell was detected in treated cells by using the AO/PI staining that confirmed that the cells had undergone remarkable morphological changes in apoptotic bodies. Furthermore, this changes in expression of caspase -8, -9 and -3 were confirmed by gene and protein quantification using RT-PCR and western blot analysis, respectively.



The current study showed that the DBID compound has demonstrated chemotherapeutic activity which was evidenced by significant increases in the expression and activation of caspase and exploit the apoptotic signaling pathways to trigger cancer cell death.
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.|Department of Biomedical Sciences, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Fatemeh
F
Hajiaghaalipour
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.|Department of Chemistry, Faculty of Science, University of Diyala, Diyala Governorate, Iraq.
Fadhil L
FL
Faraj
Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Elham
E
Bagheri
Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Hapipah M
HM
Ali
Department of Biomedical Sciences, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Mahmood Ameen
MA
Abdulla
Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Nazia A
NA
Majid
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007211:Indoles; D017382:Reactive Oxygen Species
Anticancer activity; HCT 116 cell line; colon cancer; heterocyclic compounds.; new synthetic compound; pharmacology