Derivatives of 4, 4'‐Oxydianiline Show Distinct In Vitro Cytotoxicity, Apoptosis Induction, and Selectivity against HepG2 Cancer Cells. Issue 35 (13th December 2017)

• Record Type: Journal Article
• Authors: Pillai, Vineeta; Buch, Lipi; Desai, Arpita; Singh, Vinay K.
• Is Part Of: ChemistrySelect. Volume 2:Issue 35(2017)
• Page Start: 11581
• Page End: 11589
• Publication Date: 2017-12-13
• Subjects: Apoptosis -- cell staining -- dithiocarbamate -- In vitro cytotoxicity -- metallomacrocyclic -- 4, 4′-oxydianiline; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201702296
• Languages: English
• ISSNs: 2365-6549

Abstract

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 (L 1 ‐L 3 ) was selected to derive new series of metallomacrocyclic dithiocarbamate complexes [M2 ‐ μ 2 ‐bis‐{( κ 2 S, S ‐S2 CN(R)CH2 CONHC6 H4 )2 O}] {R= Cy, M=Ni II 1a, Cu II 1 b, Zn II 1c ; R= i Pr, M=Ni II 2a, Cu II 2 b, Zn II 2c ; R= n Bu, M=Ni II 3a, Cu II 3 b, Zn II 3c }. 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 (L 1 ‐L 3 ) in their metal‐free form and metallomacrocyclic complexes, 1 a, 1 c, 2 a, 2 b, 2 c, 3 a, 3 b and3 c exhibit improved cytotoxicity than Cisplatin and selectivity against HepG2 over normal cells. Remarkably, complexes2 c (3.55 ± 0.06 μM) and3 c (2.19 ± 0.04 μM) demonstrate 21 folds to 34 folds better cytotoxic activity whereasL 3 (5.49 ± 0.04 μM), 1 a (7.27 ± 0.16 μM) and3 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). Abstract : Three diamino precursors 4, 4'‐bis(2‐(alkylamino)acetamido)diphenylether (L 1 ‐L 3 ) of a 4, 4'‐ oxydianiline was selected to derive new series of metallomacrocyclic dithiocarabamate complexes. Their potential to be substantial cytotoxic agents against HepG2 cell line, their specificity for cancer cells over normal liver cells were investigated. Assembly of number of pharmacophores on a single molecular platform evidently lead to improved therapeutic efficiencies and reduced side effects. The acridine orange/ethidium bromide (AO/EB) staining and morphological investigations clearly indicate the induction of apoptotic cell death.