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Title:	Syntesis and characterisation of organotin(IV) dithiocarbamate compounds and their cytotoxicity assessment in human leukemia cell lines
Supervisor:	Nurul Farahana Kamaludin, Dr.
Keywords:	Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia Leukemia
Issue Date:	30-May-2020
Description:	Leukemia is one of the most common cancers in Malaysia. Several drugs that are currently in use to treat leukemia are found to cause unwanted side effects. Hence, it is crucial that we study potential drugs that are more selective towards leukemia cells. In this study, six new organotin(IV) dithiocarbamate compounds with the formula R2Sn[S2CN(CH3)(C2H4C6H5)]2 where R = CH3 (C1) and C4H9 (C2), R2Sn[S2CN(C2H4OC2H5)2]2 where R = C4H9 (C3) and RnSn[S2CN(C2H5)(C6H11)]4-n where R = C4H9 (C4) and C6H5 (C5) for n = 2 and R = C6H5 (C6) for n = 3 have been successfully synthesized and characterised. All compounds displayed the presence of thioureide bands in the infrared spectra at 1466–1489 cm-1 wavelength, indicating the occurrence of partial double bond of v(C N) in dithiocarbamate group S2C NR'R”. The 13C NMR spectra displayed specific signals at δ 195.2–201.4 ppm signifying the carbon in NCS2 moiety. X-ray crystallography study showed that the ligand of C1 was coordinated to the Sn(IV) centre through anisobidentate chelating mode. These compounds were tested for their cytotoxicity and genotoxicity in human leukemia cell lines. All compounds exhibited potent cytotoxicity in K-562 and Jurkat E6-1 cell lines with IC50 values of 0.18–16.61 μg/cm3 and 0.11–4.73 μg/cm3, respectively within 24 hours by inducing apoptosis. C2 and C6 were the most potent compounds in K-562 cells with 39.87 % and 62.90 % apoptotic cells at their IC50 doses, respectively. Interestingly, C6 was selective towards the K-562 cells. The cell cycle analysis showed that C2 caused cell cycle arrest at S phase and C6 at G2/M phase after 6 hours. Genotoxicity studies via alkaline comet assay proved that C2 and C6 induced K-562 DNA damage after 3 hours with DNA tail moments of 14.30±0.91 and 19.80±1.21, respectively. Overall, these organotin(IV) dithiocarbamate compounds showed potent cytotoxicity on the leukemia cells tested by inducing DNA damage and cell cycle arrest, subsequently inducing apoptosis. In conclusion, these results demonstrate the potential of these compounds to be developed into future antileukemia agents, especially C6 as it showed potent cytotoxicity on leukemia cells and at the same time showed selectivity in non-leukemia cells.,Master's Degree in Health Science,Leukemia is one of the most common cancers in Malaysia. Several drugs that are currently in use to treat leukemia are found to cause unwanted side effects. Hence, it is crucial that we study potential drugs that are more selective towards leukemia cells. In this study, six new organotin(IV) dithiocarbamate compounds with the formula R2Sn[S2CN(CH3)(C2H4C6H5)]2 where R = CH3 (C1) and C4H9 (C2), R2Sn[S2CN(C2H4OC2H5)2]2 where R = C4H9 (C3) and RnSn[S2CN(C2H5)(C6H11)]4-n where R = C4H9 (C4) and C6H5 (C5) for n = 2 and R = C6H5 (C6) for n = 3 have been successfully synthesized and characterised. All compounds displayed the presence of thioureide bands in the infrared spectra at 1466–1489 cm-1 wavelength, indicating the occurrence of partial double bond of v(C N) in dithiocarbamate group S2C NR'R”. The 13C NMR spectra displayed specific signals at δ 195.2–201.4 ppm signifying the carbon in NCS2 moiety. X-ray crystallography study showed that the ligand of C1 was coordinated to the Sn(IV) centre through anisobidentate chelating mode. These compounds were tested for their cytotoxicity and genotoxicity in human leukemia cell lines. All compounds exhibited potent cytotoxicity in K-562 and Jurkat E6-1 cell lines with IC50 values of 0.18–16.61 μg/cm3 and 0.11–4.73 μg/cm3, respectively within 24 hours by inducing apoptosis. C2 and C6 were the most potent compounds in K-562 cells with 39.87 % and 62.90 % apoptotic cells at their IC50 doses, respectively. Interestingly, C6 was selective towards the K-562 cells. The cell cycle analysis showed that C2 caused cell cycle arrest at S phase and C6 at G2/M phase after 6 hours. Genotoxicity studies via alkaline comet assay proved that C2 and C6 induced K-562 DNA damage after 3 hours with DNA tail moments of 14.30±0.91 and 19.80±1.21, respectively. Overall, these organotin(IV) dithiocarbamate compounds showed potent cytotoxicity on the leukemia cells tested by inducing DNA damage and cell cycle arrest, subsequently inducing apoptosis. In conclusion, these results demonstrate the potential of these compounds to be developed into future antileukemia agents, especially C6 as it showed potent cytotoxicity on leukemia cells and at the same time showed selectivity in non-leukemia cells
Pages:	184
Call Number:	WH250.N853s 2020 9 tesis
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Health Sciences / Fakulti Sains Kesihatan

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