Derivatives of 4, 4’‐Oxydianiline Show Distinct In Vitro Cytotoxicity, Apoptosis Induction, and Selectivity against HepG2 Cancer Cells

Abstract

Gathering of number of pharmacophore on a single molecular platform evidently lead to improved therapeutic efficiencies and reduced side effects of conventional chemotherapy drugs. Three diamino precursors 4,4’‐bis(2‐(alkylamino)acetamido)diphenylether (L1‐L3) was selected to derive new series of metallomacrocyclic dithiocarbamate complexes [M2‐μ2‐bis‐{(κ2S,S‐S2CN(R)CH2CONHC6H4)2O}] {R=Cy, M=NiII1a, CuII 1 b, ZnII1c; R=iPr, M=NiII2a, CuII 2 b, ZnII2c; R=nBu, M=NiII3a, CuII 3 b, ZnII3c}. These were characterized by standard spectroscopic and thermogravimetric methods. MTT assay was carried out on these compounds to explore their in vitro cytotoxicity against HepG2 (hepatoma) cell line. The diamino derivatives (L1‐L3) in their metal‐free form and metallomacrocyclic complexes, 1 a, 1 c, 2 a, 2 b, 2 c, 3 a, 3 b and 3 c exhibit improved cytotoxicity than Cisplatin and selectivity against HepG2 over normal cells. Remarkably, complexes 2 c (3.55 ± 0.06 μM) and 3 c (2.19 ± 0.04 μM) demonstrate 21 folds to 34 folds better cytotoxic activity whereas L3 (5.49 ± 0.04 μM), 1 a (7.27 ± 0.16 μM) and 3 a (4.42 ± 0.06 μM) showed more than 10 fold better cytotoxic activity against HepG2 cell line as compared to the reference drug Cisplatin. Morphological evidences like shrinking of cells indicates the induction of apoptosis as part of the mechanism of action of these compounds which is further supported by the distinct staining of the cells by acridine orange/ethidium bromide (AO/EB).

Binuclear diphenyltin(IV)dithiocarbamate complexes bearing functionalized linkers: Synthesis, spectral characterization, DFT and in vitro anticancer activity

“…[26][27][28][29][30][31] The unique redox property of the sulfur atom makes it a key residue for enzyme catalysis, protein folding and redox signaling, which are important processes required for cellular energy metabolism, motility and subsistence of cellular systems. [36][37][38][39] Thus, by considering the appreciable in vitro anticancer properties of metallomacrocyclic dithiocarbamate complexes, [40][41][42][43] especially organotin(IV)dithiocarbamates macrocycles, [40] we have selected a number of diamine precursors L1-L5 (Scheme 1) to derivatize them into a new series of binuclear organotin(IV) dithiocarbamate complexes [(Ph 2 Sn) 2 -μ 2 -bis{(κ 2 S,S-S 2 CN(R) Other factors like the ease of synthesis and the effectual binding ability of dithiocarbamate ligands to an eclectic array of metal ions present in different oxidation states of transition/nontransition metal and organometallic building blocks improves the prospects of enhancing the structural modifications of anti-tumor organotin compounds.…”

Improving Cytotoxicity by Changing a Linker from Diphenylether to Diphenylmethane and now to Phenylene in Binuclear Dithiocarbamate Complexes: Synthesis and Cytotoxicity Study

“…Dapsone series of compounds showed less toxicity against primary cell line whereas these were potent against the hepatic carcinoma cell line (Hep G2) as well as glioblastoma cell lines (C6). The other reports from our lab highlighted the cytotoxic potentials of metallomacrocyclic compounds bearing biphenyl ether and diphenyl methane linker . The results showed that the compounds are potent against carcinoma (HepG2) cells whereas less toxic against normal (WRL68) cells.…”

“…Recently, we have analyzed another three series of compounds having variations on a macrocyclic ligand against hepatic cell line (WERL68) of normal origin as well as hepatic carcinoma (Hep G2). Dapsone series of compounds showed less toxicity against primary cell line whereas these were potent against the hepatic carcinoma cell line (Hep G2) as well as glioblastoma cell lines (C6).…”