title: Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells.
abstract: Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide-alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 μM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies.
authors.forename: Ali Mohd
authors.initials: AM
authors.lastname: Lone
authors.affiliation: Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu 180001, India.
authors.forename: Nawab John
authors.initials: NJ
authors.lastname: Dar
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine , Jammu 180001, India.|Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu 180001, India.
authors.forename: Abid
authors.initials: A
authors.lastname: Hamid
authors.affiliation: Department of Chemistry, University of Kashmir , Srinagar 190006, India.
authors.forename: Wajaht Amin
authors.initials: WA
authors.lastname: Shah
authors.affiliation: Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu 180001, India.
authors.forename: Muzamil
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Academy of Scientific and Innovative Research, CSIR-Indian Institute of Integrative Medicine , Canal Road, Jammu 180001, India.
authors.forename: Bilal A
authors.initials: BA
authors.lastname: Bhat
mesh_terms: D000818:Animals; D001386:Azides / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D013058:Mass Spectrometry; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D014212:Tretinoin / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001386:Azides; D014230:Triazoles; D014212:Tretinoin; D010751:Phosphopyruvate Hydratase
keywords: Retinoic acid; azide−alkyne cycloaddition; neurite outgrowth; neuroblastoma cells; neuronal markers