Synthesis and Characterisation of Bis(thiourea) Derivatives and Studies of their Biological Properties

Ainaa Nadiah, Abd Halim (2017) Synthesis and Characterisation of Bis(thiourea) Derivatives and Studies of their Biological Properties. PhD thesis, Universiti Malaysia Sarawak.

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Abstract

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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