New dibutyltin(IV) ladders: Syntheses, structures and, optimization and evaluation of cytotoxic potential employing A375 (melanoma) and HCT116 (colon carcinoma) cell lines in vitro.
Synthesis and spectroscopic properties of seven new dibutyltin(IV) compounds of 2-{(E)-4-hydroxy-3-[(E)-4-(aryl)iminomethyl]phenyldiazenyl}benzoic acids (LnHH'; n=2-8) with general formula {[Bu2Sn(LnH)]2O}2(1-7) are reported. The compounds were characterized by elemental analysis and by UV-Visible, fluorescence, IR,1H,13C and119Sn NMR spectroscopies. Solid state structures of dibutyltin(IV) compounds 1-3, 6 and 7 were accomplished from single crystal X-ray crystallography which reveal the common ladder-type structure with two endo- and two exo-Sn atoms. The redox properties of LnHH' (n=2-4, 7 and 8) and their diorganotin(IV) compounds 1-3, 6 and 7 were also investigated by cyclic voltammetry. In general, the dibutyltin(IV) derivatives exhibited significant in vitro cytotoxic potency towards A375 (melanoma) and HCT116 (colon carcinoma) cell lines as determined by several experiments, like Live and Dead assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), cleavage of caspases and PARP (poly(ADP-ribose)polymerase), and DNA fragmentation. Dibutyltin(IV) compounds increase cell death without cytolysis and decreases membrane fluidity, without interfering with p53. Among the dibutyltin(IV) compounds, compound 6 was found to be the most potent, with an IC50value of 78nM. A mechanism of action for tumor cell death is proposed.
Centre for Advanced Studies in Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong 793 022, India. Electronic address: basubaul@nehu.ac.in.
Tushar S
TS
Basu Baul
Centre for Advanced Studies in Chemistry, North-Eastern Hill University, NEHU Permanent Campus, Umshing, Shillong 793 022, India.
Dhrubajyoti
D
Dutta
School of Life & Environmental Science, Deakin University, Geelong, Victoria 3217, Australia.
Andrew
A
Duthie
Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Calcutta 700009, India.
Nikhil
N
Guchhait
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Bruno G M
BGM
Rocha
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal. Electronic address: fatima.guedes@tecnico.ulisboa.pt.
M Fátima C
MFC
Guedes da Silva
Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, India.
Raveendra B
RB
Mokhamatam
Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, India.
Nune
N
Raviprakash
Centre for DNA Fingerprinting & Diagnostics, Nampally, Hyderabad 500 001, India. Electronic address: manna@cdfd.org.in.
Sunil K
SK
Manna
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008560:Membrane Fluidity / Q000187:drug effects; D015394:Molecular Structure; D009947:Organotin Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D003603:Cytotoxins; D009947:Organotin Compounds; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
Apoptosis; Cytotoxicity; Dibutyltin(IV) ladders; Melanoma and colon carcinoma cell lines; Microviscosity; Structures