Asynthesis, Crystal Structures and in Vitro Anticancer Studies of New Thiosemicarbazone Derivatives

Abstract

Thiosemicarbazones are an important class of compounds having significant biological properties. These compounds are used as stable ligands for the synthesis of coordination compounds of biological worth. The current study describes syntheses of four new N(3)-ethyl thiosemicarbazone derivatives and their in vitro anticancer testing. The purpose of the study was to observe the effect of various subtitutions at the aromatic ring against the growth of cancerous cell. The synthesized compounds were characterized by NMR ( 1 H & 13 C) spectroscopy and the molecular structures of each of the compounds were determined using single crystal X-ray crystallographic technique. Interestingly, compound 4 appeared to have two crystallographically different units (A and B), having slightly different bond lengths and angles compared to each other. All the compounds were tested for their in vitro anticancer properties against Human Colon Cancer (HCT 116) and Breast Cancer (MCF-7) cell lines. The compounds (1-2), having halide (Cl and Br) substitutions, showed significant activity compared to those having ethoxy and allyl substitutions (3-4), indicating the possible involvement of halides against cancerous cells.

Revisiting the thiosemicarbazonecopper(II) reaction with glutathione. Activity against colorectal carcinoma cell lines

“…Recently, the effects of the interaction of ribonucleotide reductases with thioredoxin [97] and the influence of the negatively regulated miRNA-mRNA pairs [98] and ribosome-inactivating stress [99] in CRC have been discussed. Taking into account that, as previously mentioned, both ribonucleotide reductases and RNA are targets of TSCs, and previous studies show the attack of CRC cells by TSCs [100,101], it could be interesting to apply these compounds to resistant CRC cells.…”

Microwave-Assisted Synthesis of (Piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides as Potent Inhibitors of Cholinesterases: A Biochemical and In Silico Approach

“…Crizotinib ® [ 37 ], Donepezil ® [ 38 ], Risperidone ® [ 39 ], and Methyl phenidate ® [ 40 ] are the well-known examples of piperidine-based drugs ( Figure 1 ). Likewise, thiosemicarbazones are emerging scaffolds of medicinal interest and their antimicrobial [ 41 , 42 ], anti-inflammatory [ 43 ], antioxidant [ 44 , 45 ], anticancer [ 46 , 47 , 48 ], anti-Alzheimer [ 49 ], and alpha-glucosidase inhibitory [ 50 ] activities have been reported in recent years.…”

(E)-2-(2-Hydroxy-3-methylbenzylidene)-N-methylhydrazine-1-carbothioamide: supramolecular assemblies in two-dimensions mediated by N—H...S and C—H...π interactions

“…(I) 2-hydroxy-3-methylbenzylidenyl methyl 4 170 0 AWAZOP (Hussein & Guan, 2015) 5-bromo-2-hydroxybenzylidenyl methyl 1 175 12 AWEBEL (Hussein & Guan, 2015) 3-ethoxy-2-hydroxybenzylidenyl methyl 176 174 4 CIVZAK (Hussein et al, 2014b) 5-(tert-butyl)-2-hydroxybenzylidenyl ethyl 2 174 15 CIWBAN (Hussein et al, 2014b) 5-allyl-3-ethyl-2-hydroxybenzylidenyl methyl 169 173 5 DAGVOZ (Arafath et al, 2017b) 2-hydroxy-5-methoxy-3-nitrobenzylidenyl methyl 177 176 7 EFUPAX (Rubčić et al, 2008) 2-hydroxy-4-methoxybenzylidenyl phenyl 2 173 4 EROVIR (Lo & Ng, 2011) 5-chloro-2-hydroxybenzylidenyl ethyl 8 172 14 GOZQIX (Hussein et al, 2015a) 2-hydroxy-5-methoxybenzylidenyl methyl 3 175 14 GOZQIX01 (Salam et al, 2016) 2-hydroxy-5-methoxybenzylidenyl methyl 3 175 15 GOZQIX02 (Subhashree et al, 2017) 2-hydroxy-5-methoxybenzylidenyl methyl 2 175 13 HABDEW (Hussein et al, 2015c) 3-ethoxy-2-hydroxybenzylidenyl ethyl 177 176 5 HABFEY (Hussein et al, 2015c) 5-allyl-2-hydroxy-3-methoxybenzylidenyl ethyl 173, 173 176, 179 6, 8 178, 177 HAXROO (Vrdoljak et al, 2005) 2-hydroxybenzylidenyl methyl 1 176 11 HAXROO01 (Liu, 2015) 2-hydroxybenzylidenyl methyl 2 175 11 HAXSAB (Vrdoljak et al, 2005) 2-hydroxy-3-methoxybenzylidenyl methyl 177 174 5 IBAZUJ (Haque et al, 2015) 2,3-dihydroxybenzyliden methyl 1 170 1 IBEDOL (Haque et al, 2015) 2-hydroxy-5-methylbenzylidenyl methyl 3, 2 175, 173 16, 16 175, 175 IFUXEN (Tan et al, 2008b) 2,4-dihydroxybenzylidenyl ethyl 2 179 0 IFUXEN01 (Hussein et al, 2014b) 2,4-dihydroxybenzylidenyl ethyl 2 179 0 IFUXEN02 (Ramaiyer & Frank, 2015) 2,4-dihydroxybenzylidenyl ethyl 1 175 4 IFUXEN03 (Ramaiyer & Frank, 2015) 2,4-dihydroxybenzylidenyl ethyl 5 171 6 IGALUY (Tan et al, 2008c) 2,4-dihydroxybenzylidenyl methyl 5 174 9 IGALUY01 2,4-dihydroxybenzylidenyl methyl 2 177 16 IMAFIN (El-Asmy et al, 2016) 2-hydroxybenzylidenyl ethyl 1 177 13 JAJHUA (Li et al, 2016) 5-bromo-2-hydroxybenzylidenyl methyl 1 175 12 JOFHIW (Tan et al, 2008a) 2,5-dihydroxybenzyliden methyl 1 175 11 KOCLIY (Ðilović et al, 2008) 4-(diethylamino)-2-hydroxybenzylidenyl phenyl 2 172 12 LAQCIR 5-bromo-2-hydroxy-3-methoxybenzylidenyl cyclohexyl 172 177 4 NUQNAP …”