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Synthesis of Benzo[d]imidazo[2,1-b]thiazole-Propenone Conjugates as Cytotoxic and Apoptotic Inducing Agents

[ Vol. 19 , Issue. 3 ]

Author(s):

Siddiq P. Shaik, Telukutta S. Reddy, Satish Sunkari, Ayinampudi V.S. Rao, Korrapati S. Babu, Suresh K. Bhargava and Ahmed Kamal*   Pages 347 - 355 ( 9 )

Abstract:


Background: Cancer can be considered as a disease in which normal cells start behaving badly, multiplying uncontrollably, ignoring signals to stop and accumulating to form a mass that is generally termed as a tumor. Apoptosis or programmed cell death is a physiological process that enables organisms to control their cell numbers in many developmental and physiological settings and to eliminate unwanted cells and it plays essential role in chemotherapy-induced tumor-cell killing. The correct balance between apoptosis and inhibition of apoptosis is important in animal development as well as in tissue homeostasis. The aim of this paper is to introduce the readers about the design strategy and synthesis of effective cytotoxic and apoptotic inducing agents based on benzo[d]imidazo[2,1-b]thiazole scaffold.

Method: Benzo[d]imidazo[2,1-b]thiazole-propenone conjugates were synthesized by the condensation of 7- methoxy-2-(aryl)benzo[d]imidazo[2,1-b]thiazol-3-yl)prop-2-yn-1-ones with aryl/hetero aryl amines in ethanol at room temperature. These in turn were obtained from 7-methoxy-2-(aryl)benzo[d]imidazo[2,1-b]thiazole-3- carbaldehydes on treatment with ethynylmagnesium bromide followed by oxidation.

Results: 3-Arylaminopropenone linked 2-arylbenzo[d]imidazo[2,1-b]thiazole conjugates prepared in this investigation exhibited significant cytotoxic activity and arrested HeLa cancer cells in G1 phase. The treatment of the conjugate led to 40% of loss of mitochondrial membrane potential (DΨm) in HeLa cells and 4 fold increase in the levels of reactive oxygen species (ROS). In addition, it induces apoptosis in HeLa cells, this was examined by the wound healing assay, Actin filaments and Hoechst staining assay.

Conclusion: The encouraging biological profile exhibited by these 3-arylaminopropenone 2-aryl linked benzo[d]imidazo[2,1-b]thiazole conjugates demonstrate that they have the potential to be developed as a lead by further structural modifications to obtain potential chemotherapeutic agents that are likely to target the HeLa cancer cells.

Keywords:

Benzo[d]imidazo[2, 1-b]thiazole, cytotoxicity, apoptosis, mitochondrial membrane depolarization, ROS.

Affiliation:

Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007, Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500007



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