Proceedings of MatricesFor IITTEP – ICoMaNSEd 2015
ISBN: 978-602-74204-0-3
Chemistry Page 130
STRUCTURE-ACTIVITY RELATIONSHIP SAR OF ENDOCYTOSIS INHIBITORS
Dian H.O. Howan
1 1
Chemistry Department, Faculty of Mathematics and Natural Science, State University of Manado, Minahasa, Indonesia
dian_octorinayahoo.com
Abstract: Endocytosis is the process of cells take up extracellular materials and recycles their membrane. This
process happens in almost all living eukaryotic cells by several mechanisms that can be divided into two types, namely: phagocytosis, and pinocytosis. Endocytosis plays significant roles in many
pathological conditions. There are over 100 known diseases involving endocytosis and intracellular trafficking. A number of endocytosis researches has been conducted, and generated some compounds
with great inhibitor value. The inhibitors namely: dynasore, bis-T, MiTMAB, Indole analogues, and phthalamide analogues. This paper will discuss the structure-activity relationship profiles of these
inhibitors. Keywords: Endocytosis, structure-actity relationship, inhibitors, dynamin
1. Introduction
Endocytosis is the process whereby cells take up extracellular material and recycle their membranes Cousin
et al
, 2001. It happens in almost all living eukaryotic cells by several mechanisms that can be divided into two types, namely, phagocytosis, which occurs only in
specialised mammalian cells and pinocytosis, which occurs in all cells is regulated by intracellular and extracellular signals Liu
et al
, 1995; Conner
et all
, 2003. Phagocytosis is the process that occurs when cells uptake the large particles, while pinoctytosis is the process
of taking up fluid and solutes. Furthermore, pinocytosis can be divided into two mechanisms, clathrin mediated endocytosis CME and clathrin-independent endocytosis Liu
et al
, 1995. One of enzymes that involves in endocytosis process is dynamin Mousavi
et al
, 2004.
2. Endocytosis, Dynamin and Diseases
Endocytosis plays significant roles in many of human pathological conditions. There are over 100 known diseases involving endocytosis and intracellular trafficking Aridor Hannan,
2002; Aridor Hannan, 2000.. Control of endocytosis through the inhibition of dynamin could be useful in the treatment of cancer; viral, bacterial and other pathogenic infections;
immunodeficiency, gastrointestinal, neurodegenerative, neurological and kidney diseases. Several studies revealed some diseases that are connected to dynamin, such as Charcot-Marie-
Tooth CMT disease Zuchner
et al
, 2005, Centronulear myopathy CNM Bitoun
et al
, 2005, and Papillomaviruses, HPV16 and BPV1
– the etiologic agent of cervical and anal cancers and of tumors and disease in animals Abban
et al
, 2008 Several neurodegenerative diseases are associated with dynamin-dependent endocytic
trafficking pathways. These include Alzheimer’s disease, Huntington’s disease HD, stiff- person syndrome, Lewy body dementians, and Niemann-Pick type C disease Aridor
Hanna n, 2002. The presynaptic α-synuclein protein is believed to be involved in Lewy body
diseases, including Parkinson’s disease, Lewy body dementia and a Lewy body variant of
Proceedings of MatricesFor IITTEP – ICoMaNSEd 2015
ISBN: 978-602-74204-0-3
Chemistry Page 131
Alzheimer’s disease Sung
et al
, 2001. Furthermore, these pathologies were found to be a direct consequence of α-synuclein endocytosis suggesting that endocytosis inhibitors may be
useful in the treatment of α-synuclein related disorders.
3. Structur-Activity Relationship SAR of Dynamin Endocytosis Inhibitors