Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases
There is an urgent need for substantial investigation of non-platinum drugs with higher activity and improved selectivity to address the problem associated with the use of platinum-based compounds as therapeutic agents. In light of this, diphenyltin(IV), dimethyltin(IV) and tin(IV) compounds were...
| Main Author: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2019
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| Online Access: | http://psasir.upm.edu.my/id/eprint/90030/1/FS%202020%205%20ir.pdf |
| _version_ | 1796982238965923840 |
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| author | Md Yusof, Enis Nadia |
| author_facet | Md Yusof, Enis Nadia |
| author_sort | Md Yusof, Enis Nadia |
| collection | UPM |
| description | There is an urgent need for substantial investigation of non-platinum drugs with
higher activity and improved selectivity to address the problem associated with the
use of platinum-based compounds as therapeutic agents. In light of this,
diphenyltin(IV), dimethyltin(IV) and tin(IV) compounds were synthesised from the
Schiff bases of three series of dithiocarbazate (S-2-methylbenzyldithiocarbazate
(S1), S-4-methylbenzyl dithiocarbazate (S2), S-benzyldithiocarbazate (S3)) and
two series of thiosemicarbazides (4-methyl-3-thiosemicarbazide and 4-phenyl-3-
thiosemicarbazide) with aldehydes, 2-hydroxy-3-methoxybenzaldehyde (oVa) or
2,3-dihydroxybenzaldehyde (catechol). The tin(IV) compounds formed were found
to have a general formula of [R2Sn(ONS)] and [Sn(ONS)2] (where R = Me and Ph).
The compounds were fully characterised by physico-chemical and spectroscopic
methods. The spectroscopic results supported the coordination geometry in which
the Schiff bases behaved as tridentate ONS donor ligands coordinating via
azomethine nitrogen, thiolo sulphur and phenoxide oxygen atoms. A total of 11
crystal structures of the expected compounds were solved in this work. In order to
verify the experimental data, the compounds were optimised using the density
functional theory (DFT) method with the B3LYP hybrid exchange correlation
functional with LanL2DZ pseudopotential on tin and 6-311G(d,p) Pople basis set
for all other atoms. Diphenyltin(IV) compounds showed the most promising
cytotoxicity with IC50 values ranging between 0.016 – 4.40 μM against a panel of
twelve cancer cell lines (RT-112, EJ-28 (bladder), HT29 (colon), U87, SJ-G2, SMA
(glioblastoma), MCF-7 (breast), A2780 (ovarian), H460 (lung), A431 (skin), Du145
(prostate), BE2-C (neuroblastoma) and MIA (pancreatic)). The three
diphenyltin(IV) compounds of the oVa series were able to induce the production
of Reactive Oxygen Species (ROS) and acted as a cell apoptosis inducer. Good
binding interactions for all the diphenyltin(IV) compound series were observed and supported by molecular docking analysis, where hydrogen, electrostatic and
hydrophobic binding interactions were observed. This highlights the important of
two phenyl groups coordinated directly to the tin ion to enhance the cytotoxicity by
strong π-π stacking interactions to biomacromolecules. Diphenyltin(IV)
compounds could bring hope in the field of drug development against various
diseases including cancers. |
| first_indexed | 2024-03-06T10:49:05Z |
| format | Thesis |
| id | upm.eprints-90030 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T10:49:05Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | upm.eprints-900302021-12-03T01:30:14Z http://psasir.upm.edu.my/id/eprint/90030/ Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases Md Yusof, Enis Nadia There is an urgent need for substantial investigation of non-platinum drugs with higher activity and improved selectivity to address the problem associated with the use of platinum-based compounds as therapeutic agents. In light of this, diphenyltin(IV), dimethyltin(IV) and tin(IV) compounds were synthesised from the Schiff bases of three series of dithiocarbazate (S-2-methylbenzyldithiocarbazate (S1), S-4-methylbenzyl dithiocarbazate (S2), S-benzyldithiocarbazate (S3)) and two series of thiosemicarbazides (4-methyl-3-thiosemicarbazide and 4-phenyl-3- thiosemicarbazide) with aldehydes, 2-hydroxy-3-methoxybenzaldehyde (oVa) or 2,3-dihydroxybenzaldehyde (catechol). The tin(IV) compounds formed were found to have a general formula of [R2Sn(ONS)] and [Sn(ONS)2] (where R = Me and Ph). The compounds were fully characterised by physico-chemical and spectroscopic methods. The spectroscopic results supported the coordination geometry in which the Schiff bases behaved as tridentate ONS donor ligands coordinating via azomethine nitrogen, thiolo sulphur and phenoxide oxygen atoms. A total of 11 crystal structures of the expected compounds were solved in this work. In order to verify the experimental data, the compounds were optimised using the density functional theory (DFT) method with the B3LYP hybrid exchange correlation functional with LanL2DZ pseudopotential on tin and 6-311G(d,p) Pople basis set for all other atoms. Diphenyltin(IV) compounds showed the most promising cytotoxicity with IC50 values ranging between 0.016 – 4.40 μM against a panel of twelve cancer cell lines (RT-112, EJ-28 (bladder), HT29 (colon), U87, SJ-G2, SMA (glioblastoma), MCF-7 (breast), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic)). The three diphenyltin(IV) compounds of the oVa series were able to induce the production of Reactive Oxygen Species (ROS) and acted as a cell apoptosis inducer. Good binding interactions for all the diphenyltin(IV) compound series were observed and supported by molecular docking analysis, where hydrogen, electrostatic and hydrophobic binding interactions were observed. This highlights the important of two phenyl groups coordinated directly to the tin ion to enhance the cytotoxicity by strong π-π stacking interactions to biomacromolecules. Diphenyltin(IV) compounds could bring hope in the field of drug development against various diseases including cancers. 2019-12 Thesis NonPeerReviewed text en http://psasir.upm.edu.my/id/eprint/90030/1/FS%202020%205%20ir.pdf Md Yusof, Enis Nadia (2019) Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases. Doctoral thesis, Universiti Putra Malaysia. Organotin compounds Schiff bases Tin compounds |
| spellingShingle | Organotin compounds Schiff bases Tin compounds Md Yusof, Enis Nadia Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title | Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title_full | Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title_fullStr | Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title_full_unstemmed | Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title_short | Synthesis, structural characterisation and cytotoxicity study of tin(IV) compounds containing ONS Schiff bases |
| title_sort | synthesis structural characterisation and cytotoxicity study of tin iv compounds containing ons schiff bases |
| topic | Organotin compounds Schiff bases Tin compounds |
| url | http://psasir.upm.edu.my/id/eprint/90030/1/FS%202020%205%20ir.pdf |
| work_keys_str_mv | AT mdyusofenisnadia synthesisstructuralcharacterisationandcytotoxicitystudyoftinivcompoundscontainingonsschiffbases |