 Corresponding author: Nitin Kumar Neuro-pharmaceutical Research Laboratory, Dr. B.R. Ambedkar Centre For Biomedical Reaserch (ACBR), University of Delhi, Delhi, 110007, India. Copyright © 2022 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Synthesis and anticancer activity evaluation of substituted carbazole bearing thiosemicarbazide derivatives against human glioma U87 MG cell line Nitin Kumar * , Vishal Nemaysh and Pratibha Mehta Luthra Neuro-pharmaceutical Research Laboratory, Dr. BR. Ambedkar Centre for Biomedical Research (ACBR), University of Delhi, 110007, India. World Journal of Advanced Research and Reviews, 2022, 16(03), 884–892 Publication history: Received on 11 November 2022; revised on 21 December 2022; accepted on 24 December 2022 Article DOI: https://doi.org/10.30574/wjarr.2022.16.3.1402 Abstract Both carbazole and thiosemicarbazide scaffold showed various potential biological activities in medicinal chemistry. In this research work, we synthesized a series of carbazole bearing thiosemicarbazide derivatives (17-28) and evaluated thier in vitro cytotoxicity (IC50) profile on the U87 MG cell line using MTT assay. All target compounds were well characterized by NMR and HRMS mass spectroscopy. In series, six compounds (17, 20, 21, 22, 23, 28) found better in vitro cytotoxicity (IC50) values were 26.50 μM, 34.0 μM, 39 μM, 80 μM, 62 μM, 50 μM respectively compare to standard drug Temozolomide (IC50 = 100 μM). The SAR study of all final compounds (17-28) were also analyzed on the basis of different substituents on 6th position of carbazole scaffold bearing thiosemicarbazide derivatives against U87 MG cell line. All of the above studies showed that carbazole bearing thiosemicarbazide derivatives (17-28) showed anticipated anticancer activity against U87 MG glioma cell line. Keywords: GBM (Glioblastoma); Carbazole; Thiosemicarbazide; TMZ (Temozolomide); Compound 17((E)-2-((1,4- dimethyl-9-H-carbazol-3-yl)methylene)hydrazinecarbothioamide); SAR (Structure activity relationship); MTT (tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) 1 Introduction Glioblastoma multiforme (GBM) is a type IV grade tumor according to WHO grading and classification [1,2]. GBM is a most deadly, aggressive and undifferentiated type of tumor originated from glial cell in the brain. The current treatment standard is a multimodal approach combining neurosurgery, fractionated radiation therapy, and chemotherapy [3, 4]. However, GBM patients usually have a median survival of approximately 14 to 15 months from the diagnosis [3]. Temozolomide (TMZ), is the only anticancer drug has been reported to improve the survival in a phase III study of GBM when administered concomitant with the radiotherapy [5]. Carbazole derivatives showed potential biological and photophysical properties [6-11]. Carbazole derivatives can target DNA structures and has prospective for development into anticancer drugs [6, 9]. Carbazole, a tricyclic planar structure, makes it prone to interact with DNA either via intercalation or minor groove binding well established in literature[9- 11]. 1,4-Dimethyl-9-H-carbazole structure part is present in Ellipticine (5,11-dimethyl-6-H-pyrido[4,3-b]carbazole), acts as an intercalative agent and blocks topoisomerase II activity only [6, 9, 12] Anna Caruso et al. designed and synthesized 3,6 substituted carbazole linked to guanidine derivatives ( 1) showed potential in vitro cytotoxicity (IC50) value 3.1 μM against HL-60 cell line [12]. Earlier our group reported substituted bis carbazole derivatives (2) showed potential in vitro cytotoxicity (IC50) against human glioma U87 MG cell line[9]. G.A. Ciftci et al. reported apoptotic effect of compound 2-[(9-ethyl-9H-carbazol-3-yl)amino]-2-oxoethyl N,N-disubstituted dithiocarbamates (3) showed good in