Synthesis, Characterisation and Biological Activity Screening Of Schiff Base Ligands Containing Isatin and Their Metal Complexes

Six new Schiff bases formed from the condensation reaction of S-benzyldithiocarbazate (SBDTC) and S-methyldithiocarbazate (SMDTC) with selected diketones containing isatin derivatives namely isatin, 5-fluroisatin, 5-chloroisatin, 5-bromoisatin and methylisatin have been synthesised. Complexes of cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) with these Schiff bases were prepared. These compounds were characterised by elemental analyses and various physico-chemical techniques. Single crystal X-ray analyses were carried out on five different compounds. X-ray crystallographic study of SB5ClISA and SB5BrISA Schiff bases proved that the condensation reaction between S-benzyldithiocarbazate with the isatin derivatives occur at the carbonyl position number 3 in the isatin ring. Crystal structure analyses of Co(II) and Ni(II) complexes showed that [Ni(SMISA)2]·MeCN and [Co(SMISA)2]·MeCN are six-coordinate and have a distorted octahedral structure with the ligands coordinated to the metal ions as uninegatively charged tridentate chelating agents via the azomethine nitrogen, thiolate sulphur atom and carbonylic oxygen atoms of the isatin moiety. Crystal structure of the Cu(SMISA)2 complex exhibited distorted square planar geometry with the ligands coordinated to the metal ion as uninegatively charged bidentate ions through the azomethine nitrogen and thiolate sulphur atoms. Unfortunately, none of the Zn(II) and Cd(II) complexes produced single crystals but, it is proposed, that they are also four-coordinated with a tetrahedral geometry. The Schiff bases and their metal complexes were evaluated for cytotoxic and antimicrobial activity. Cytotoxic screening was carried out against human breast cancer cells with positive estrogen receptor (MCF-7) and human breast cancer cells with negative estrogen receptor (MDA-MB-231). Some of the Schiff bases and metal complexes were found to be very active against these breast cancer cell lines with a CD50 values lower than Tamoxifen. Antimicrobial screening was carried out against four bacteria and three fungi. All compounds were found to have low or no activity against the selected bacteria and fungal strains

First syntheses of fluoromuscimols

Chapter 1 provides a general introduction on the role of bioisosterism of fluorine aiming to improve the pharmacokinetics properties of lead compounds. GABAA receptors specifically, synaptic GABAA receptors, extrasynaptic GABAA receptors and GABAA rho receptors are then presented. Compounds that exhibit agonist and partial agonist effects at these receptors are also discussed. The applications of some compounds as GABAA receptor PET radiotracers are also described. Chapter 2 details the synthesis of two fluorinated analogues of muscimol, fluoromuscimol and trifluoromethylmuscimol. Fluoromuscimol was obtained from the lithiation of a Boc-protected isoxazole followed by in-situ fluorination using NFSI, whereas trilfuoromethylmuscimol was obtained from the coupling of a heteroaryl iodide with trifluoromethylcopper species, which was generated in-situ from MFSDA in the presence of CuI. Fluoromuscimol and trifluoromethylmuscimol were assessed on human synaptic, (α₁β₂γ₂), extrasynaptic, (α₄β₂δ) and ρ₁ subunits of the GABAA receptor. The biological results show that fluoromuscimol exhibits greater maximum response in comparison to GABA at the extrasynaptic GABAA receptors (α₄β₂δ), but lower overall potency, whereas trifluoromethylmuscimol was inactive at all the tested GABAA receptors. Chapter 3 discusses the synthesis and late stage fluorination of diaryliodonium salts as precursors to fluoromuscimol. Application of iodonium salts as precursors for nucleophilic fluorination in PET studies are also highlighted. The last part of this chapter focuses on the synthesis of iodomuscimol as a potential alternative SPECT radiotracer to fluoromuscimols in probing GABA binding sites on GABAA receptors

Synthesis, characterization and biological activity of NitrogenOxygen-Sulfur (NOS) transition metal complexes derived from novel s-2,4-dichlorobenzyldithiocarbazate with 5-fluoroisatin / Mohd Abdul Fatah Abdul Manan ... [et al.]

A novel Schiff base containing nitrogen-oxygen-sulfur (NOS) donor atoms formed from the condensation reaction of S-2,4dichlorobenzyldithiocarbazate (S-2.4BDTC) with 5-fluroisatin has been synthesized. Complexes of cobalt(ll), nickel(ll), copper(ll), zinc(ll) and cadmium(ll) with this Schiff base have been prepared and characterized using elemental analysis and various physico-chemical techniques. In the cobalt(ll) andnickel(II) complexes the SchifJbase behaves as a uninegatively charged tridentate nitrogen-oxygen-sulfur (NOS) chelating ligand, bonding through the azomethine nitrogen, thiolate sulfur and carbonylic oxygen of the isatin moiety. However. in the copper(ll), zinc(II) and cadmium(II) complexes the Schiff base behaves as a nitrogen-sulfur (NS) bidentate chelating ligand, bonding through the azomethine nitrogen and thiolate sulfur. The Schiff base and the metal complexes were evaluated with respect to antimicrobial activity, which was performed in reallion to two selected pathogenic microbials (Bacillus subtilis and Pseudomonas aeruginosa). It was observed that only the zinc Schiffbase complex exhibited strong activity against the Bacillus subtilis bacteria with an inhibition zone of 25 mm

A crystallographic study of S-methyl 2-(5-chloro-2-oxoindolin-3-ylidene)hydrazinecarbodithioate

S-methyl 2-(5-chloro-2-oxoindolin-3-ylidene) hydrazinecarbodithioate (SM5ClISA) has been prepared from S-methyldithiocarbazate and 5-chloroisatin. The compound crystallized in monoclinic crystal system with space group P 21/n, Z = 4, V = 1201.85(7) Å3 and unit cell parameters a = 6.5466(2) Å, b = 7.5056(3) Å, c = 24.6509(8) Å, α = γ = 90° and β = 97.1434(18)°. The crystal structure reveals that the compound exists in the thione form with the chlorine occupies the fifth position in the isatin ring with the bond length of 1.739(2) Å. The 5-chloroisatin moiety is trans with respect to the C3–N2 and C3–S4 bonds whereas the methyl group of the dithiocarbazate moiety is cis with respect to the C3–N2 and C3–S5 bonds

The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists

MAFAM acknowledges the Ministry of Education of Malaysia and Universiti Teknologi MARA for a scholarship. MC acknowledges the funding support of the Australian National Health and Medical Research Council (APP1081733).Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor.PostprintPostprintPeer reviewe

Synthesis, characterisation and antibacterial activity of Schiff base derived from S-methyldithiocarbazate and methylisatin.

New tridentate nitrogen–oxygen–sulfur Schiff base has been prepared from the condensation reaction of S-methyldithiocarbazate and methylisatin. The compound crystallized in triclinic crystal system with space group P − 1, Z = 2, V = 612.92(3) Å3 and unit cell parameters a = 6.8540(2) Å, b = 8.3022(2) Å, c = 11.5243(4) Å, α = 79.8186(13)°, β = 90.5224(14)° and γ = 72.1362(13)°. Crystal structure reveals that the compound exists in the thione form with the methylisatin moiety is trans with respect to the C3–N2 and C3–S4 bonds whereas the methyl group of the dithiocarbazate moiety is cis with respect to the C3–N2 and C3–S5 bonds. The Schiff base was found to be selectively active against the selected Gram positive bacterial strains (Bacillus subtilis and Staphylococcus aureus) with the inhibition zones of 16 and 12 mm, respectively

The crystal structure and cytotoxicity of centrosymmetric copper(II) complex derived from S-methyldithiocarbazate with isatin.

Copper(II) complex of S-methyldithiocarbazate with isatin has been prepared and screened for their cytotoxic activities against MCF-7 (Human non-metastatic mammary gland adenocarcinoma cell line) and MDA-MB-231 (Human metastatic mammary gland adenocarcinoma cell line). The compound crystallized in an orthorhombic crystal system with a space group C 2cb and was found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line with an IC50 value 0.45 μg/mL. The crystal structure of this centrosymmetric Cu(SMISA)2 complex (SMISA = Schiff base formed by condensation reaction of S-methyldithiocarbazate with isatin) showed that the copper atom has a distorted square-planar geometry with the Schiff base coordinated to the metal ion as a uninegatively charged bidentate ligand through the azomethine nitrogen and thiolate sulfur

Synthesis, crystal structure and Hirshfeld surface analysis of ethyl 4-hydroxy-2-(4-hydroxyphenyl)-1-methyl-5-oxo-2,5-dihydro- 1H-pyrrole-3-carboxylate

Ethyl 4 hydroxy-2-(4-hydroxyphenyl)-1-methyl-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylate, C14H15NO5 (1) was synthesized via multicomponent reaction (MCR) of sodium diethyl oxalacetate, methylamine, and 4-hydroxybenzaldehyde. The structure of 1 was elucidated by using FT-IR, NMR and GCMS. These results were further confirmed by means of single crystal X-ray crystallography. The results showed that 1 was crystallized in orthorhombic space group Pca21 where a = 17.102(4), b = 9.923(2), c = 16.037(4), Å. The quantification of intermolecular interactions in the crystal structure was obtained by Hirshfeld surface analysis and showed that the H•••H contacts were the most dominant interactions

Synthesis, characterization and cytotoxic activity of S-benzyldithiocarbazate Schiff bases derived from 5-fluoroisatin, 5-chloroisatin, 5-bromoisatin and their crystal structures

Schiff bases were prepared from S-benzyldithiocarbazate with 5-fluro-, 5-chloro- and 5-bromoisatin. All are potential tridentate nitrogen, oxygen, sulfur donors. They were found to be selectively active against MCF-7 cell line (Human non-metastatic mammary gland adenocarcinoma cell line). The bromide and fluoride compounds were the most active with IC50 values of 6.40 μM (2.6 μg/mL) and 9.26 μM (3.2 μg/mL) respectively while the chloride derivative was weakly active with an IC50 value of 38.69 μM (14.0 μg/mL). The cytotoxic activity of the halo substituted isatins against the breast cancer cell lines tested is in the order of Br > F > Cl. Planarity of the isatin ring in the Schiff bases can be arranged in the following order SB5FISA > SB5ClISA > SB5BrISA while the perpendicularity of the benzyl ring towards the dithiocarbazate plane can be ordered as follows, SB5FISA > SB5BrISA > SB5ClISA

Cadmium(II) Schiff base complex containing 5-fluoroisatin moiety:synthesis, characterization, antibacterial activity and structural studies

Financial support is acknowledged from Universiti Teknologi MARA.The Schiff base ligand, HSB5FISA ( H1 ), obtained by the condensation of S-benzyldithiocarbazate with 5-fluoroisatin, has been employed to synthesize a new cadmium(II) complex, Cd(SB5FISA)2 ( 2 ) (SB5FISA = monoanionic form of H1 ). The complex has been characterized by elemental analysis, molar conductivity, magnetic susceptibility, inductively coupled plasma atomic emission spectroscopy (ICP-AES), Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet-visible spectroscopy (UV-Vis). The crystallographic study of Cd(SB5FISA)2•2DMSO ( 2a ) (DMSO = dimethyl sulfoxide) was conducted using single-crystal X-ray diffraction. The crystal structure of 2a confirmed the presence of six-coordinated cadmium in a distorted octahedral environment. Ligand H1 behaves in a tridentate monoanionic fashion, coordinating to a cadmium(II) metal centre through the thiolate sulfur, azomethine nitrogen and carbonyl oxygen. The antibacterial activity of both H1 and 2 was examined against four different bacterial strains using the disc diffusion method. Complex 2 showed significant inhibitory effect against Bacillus subtilis with an inhibition zone of 14 mm, comparable to the standard antibiotic streptomycin.Publisher PDFPeer reviewe