Synthesis and Characterisation of Bis(thiourea) Derivatives and Studies of their Biological Properties
Five series of novel bis(thiourea) derivatives 41a-e, 42a-l, 43a-f, 46a-c and 50a-f bearing different pharmacophores have been successfully synthesised via nucleophilic substitution reaction of benzene-1,4-dicarbonyl isothiocyanate intermediate 52 with various amines derivatives. Preparations of...
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| Format: | Thesis |
| Language: | English |
| Published: |
2017
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| Subjects: | |
| Online Access: | http://ir.unimas.my/id/eprint/23866/5/Ainaa%20Nadiah.pdf |
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| Summary: | Five series of novel bis(thiourea) derivatives 41a-e, 42a-l, 43a-f, 46a-c and 50a-f bearing
different pharmacophores have been successfully synthesised via nucleophilic substitution
reaction of benzene-1,4-dicarbonyl isothiocyanate intermediate 52 with various amines
derivatives. Preparations of 42a-l and 43a-f in acetonitrile at room temperature produced
higher yields compared to the reaction in acetone reflux. The structures of all the synthesised
compounds were elucidated using elemental CHN analysis, FT-IR, 1H and 13C NMR
spectroscopies and corresponded to the proposed molecular structures. The antibacterial
activities of the synthesised compounds were evaluated against bacteria Escherichia coli and
Staphylococcus aureus, while antioxidant activities were studied employing DPPH assay. In
the 1st series of bis(thiourea) (41a-e), 41c bearing phenyl group exhibited excellent
antibacterial activities against E. coli with minimum inhibitory concentration (MIC) of 175
ppm. While, antibacterial studies on the 2nd series of bis(thiourea) (42a-l), bearing
halogenated anilines at ortho, meta and para positions, demonstrated that halogens at ortho
position (42d and 42g) also exhibited excellent activities against E. coli and S. aureus in
comparison to the standard ampicillin. The 3rd series of bis(thiourea) (43a-f), bearing methyl
and methoxy to the phenyl group at different positions were inactive towards both bacteria.
Antibacterial screening on bis(thiourea) bearing long alkyl chains (46a-c) showed 46a and
46b displayed excellent activity against E. coli with MIC of 135 and 145 ppm respectively,
while 46c bearing C14 alkyl chain was acted as cutoff point with no antibacterial properties.
Bis(thiourea)-azo 50a-f possessing phenolic group were tested for antioxidant activities. paraSubstituted halogens (50c and 50f) demonstrated good antioxidant activity with IC50 of 105.5
ppm and 122 ppm respectively, while ortho-substituted halogen (50d) showed moderate
activity with IC50 of 148 ppm in comparison to ascorbic acid as a standard (IC50 = 14.2 ppm).
iv
The resonance effect of the halogens substituents stabilised the radical intermediate and
enhanced the antioxidant activities. The presence of two folds of N-H, C=O and C=S as well
as other substituents in the molecular structure of the synthesised compounds played
important roles to the enhancement of the biological properties. The ability of these groups to
easily protonated under acidic condition and reacted with the carboxyl and phosphate groups
of the bacterial surface further enhanced the antibacterial activities. |
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