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• 91-56-5 indole-2,3-dione 
• 6610-29-3 4-methylthiosemicarbazide 
• 6610-29-3 1-amino-3-methylisothiourea 

Relevant academic research and scientific papers

Synthesis, structure and cytotoxicity evaluation of complexes of N1-substituted-isatin-3-thiosemicarbazone with copper(I) halides

Synthesis of Isatin-N1-methyl-thiosemicarbazone (H2itsc-N1-Me, H2L1) and isatin-N1-ethyl-thiosemicarbazone (H2itsc-N1-Et, H2L2) has been carried out and the effect of substituents (at N1 atom of isatin-3-thiosemicarbazones) on nuclearity of copper(I) halide complexes has been investigated. Reactions of copper(I) halides (X = I, Br, Cl) with H2L1 and H2L2 using Ph3P as co-ligand in 1:1:1 (M:L:PPh3) molar ratio in acetonitrile yielded complexes of stoichiometry [CuX(H2L1)(Ph3P)] (X = I, C1; Br, C2; Cl, C3) and [CuX(H2L2)(Ph3P)] (X = I, C4; Br, C5; Cl, C6) respectively. All these complexes have been characterized using analytical and spectroscopic data (IR, 1H NMR and ESI mass). The single crystal structure has been solved for H2L1 and C2. The complex C2 has distorted tetrahedral geometry around copper(I) and isatin-N1-methyl-thiosemicarbazone coordinated to metal center as neutral, bidentate, N3, S-chelating ligand. Elemental analysis suggested the presence of one acetonitrile molecule in complexes C3 and C6 and half CH3CN in complexes C2 and C4 as solvent of crystallization. MTT assay, supported by docking studies have revealed the cytotoxic nature of the compounds C1-C6.

Spectroscopic, DNA cleavage and antimicrobial studies of Co(II), Ni(II) and Cu(II) complexes of sulfur donor schiff bases

A series of Co(II), Ni(II) and Cu(II) complexes of the type ML2 of Schiff bases derived from methylthiosemicarbazide and isatin/chloroisatin have been synthesized. Schiff bases exhibit thiol-thione tautomerism wherein sulfur plays an important role in the coordination. In view of analytical, spectral (IR, NMR, UV-vis, ESR, FAB-Mass) and magnetic studies, it has been concluded that all the metal complexes possess octahedral geometry. The measured molar conductance values in DMF indicate that the complexes are non-electrolytes in nature. The redox behaviors of the metal complexes are investigated by using cyclic voltammetry. The Schiff bases and their metal complexes have been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi) and antifungal activities (Aspergillus niger, Aspergillus flavus and Cladosporium) by the minimum inhibitory concentration method. The DNA cleavage studies showed the cleavage of DNA by the agarose gel electrophoresis method.

Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase

A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus. The new synthesized compounds are active towards both DNA polymerase and ribonuclease H in the μM range. The nature of the aromatic group in the position 4 of the thiazole was relevant in determining the biological activity.

Back to the coordination modes of the thiosemicarbazonate chain: New insights from diorganolead(IV) and lead(II) derivatives of isatin-3- thiosemicarbazone

The syntheses and characterizations of the new heteroleptic complexes [PbPh2(OAc)(N2-L1)]?MeOH?EtOH, [PbPh2(OAc)(N3-L2)]?H2O, [Pb(OAc)(N2-L1)], [Pb(OAc)(N3-L 1)]?3H2O and [Pb(OAc)(N2-L2)] {HL1 = isatin-3-thiosemicarbazone, HL2 = isatin-3-(N 1-methylthiosemicarbazone); N2-Lx = thiosemicarbazonate bound through O,S and the hydrazinic [N(2)] nitrogen atom; N3-Lx = thiosemicarbazonate bound through the O,S and the iminic [N(3)] nitrogen atom} are described. The single-crystal X-ray structures of HL2, [PbPh2(OAc)(N2-L1)] ?MeOH?EtOH, [PbPh2(OAc)(N3-L2)] ?H2O, [Pb(OAc)(N2-L1)] and [Pb(OAc)(N 3-L1)]?3H2O have been solved. The organometallic compounds [PbPh2(OAc)(N2-L 1)]?MeOH?EtOH and [PbPh2(OAc)(N 3-L2)]?H2O have a roughly similar distorted bipyramidal pentagonal stereochemistry, with apical phenyl groups and both the O,Nx,S-coordinated Lx- and the anisobidentate AcO- ligands in the equatorial plane. In [PbPh2(OAc) (N2-L1)]?MeOH?EtOH, the (N2-L 1)- ligand forms a four- and a six-membered chelate ring with the metal, whereas in PbPh2(OAc)(N3-L 2)]?H2O the two chelate rings formed by (N 3-L2)- are five-membered. The PbII complexes, [Pb(OAc)(N2-L1)] and [Pb(OAc)(N 3-L1)], which were isolated from the same solution, are linkage isomers. These compounds have a rather irregular stereochemistry that suggests the presence of a stereochemically active lone electron pair; in [Pb(OAc)(N2-L1)] the (L1)- ligand is O,N2,S-coordinated and in [Pb(OAc)(N3-L1)] this ligand is O,N3,S-coordinated. Analyses of all these systems in solution by 1H and 13C NMR spectroscopy showed that during synthesis the kinetically controlled O,N2,S isomer formed first due to the rigidity of the ligand. If the compound remains in solution, slow partial evolution to the O,N3,S isomer occurs. DFT calculations predict that [Pb(OAc)(N3-L1)] is slightly more stable than [Pb(OAc)(N2-L1)] both in the gas phase and in DMSO solution. The calculations also modelled structures for the two isomers close to those obtained by X-ray diffraction studies. Solid state and solution studies indicated that, in the title derivatives, the thiosemicarbazone chain is initially bound by N2,S coordination, but evolves with time to form the N3,S-linkage isomer.

Synthesis, characterization and anti-tubercular activity of substituted thiosemicarbazones and their ni(ii) complexes

Complexes of substituted isatin-3-thiosemicarbazones (H2itsc-N1-Me, H1L; H2itsc-N1-Ph, H2L) and substituted indole-3-thiosemicarbazone (HIntsc-N1-Ph, H3L) with Ni (II) and triphenylphoshine of formula, [NiCl(L)(Ph3P)] (anionic form of L = 1L, 1; 2L, 2, 3L, 3) have been synthesized. The ligands and complexes have been characterized using spectroscopic techniques (IR, 1H NMR). 1HNMR of complexes supports binding of thio- ligands in anionic form. All the ligands (H1L - H3L) and their complexes were evaluated for their antitubercular activities. The enhancement in anti-TB activity of ligands on complexation with Ni(II) has been observed.

Insight on a new indolinone derivative as an orally bioavailable lead compound against renal cell carcinoma

A series of novel 3-indolinone-thiazolidinones and oxazolidinones 4a-k was synthesized via molecular hybridization approach and sequentially evaluated to explore its cytotoxic activity. The cytotoxicity screening pointed toward the N-cyclohexyl thiazolidinone derivative 4f that revealed promising renal cytotoxicity against CAKI-1 and UO-31 renal cancer cell lines with IC50 values 4.74 and 3.99 μM, respectively, which were comparable to those of sunitinib along with good safety threshold against normal renal cells. Further emphasis on compound 4f renal cytotoxicity was achieved via different enzyme assays and CAKI-1 and UO-31 cell cycle analysis. The results were supported by in silico studies to explore its physicochemical, pharmacokinetic and drug-likeness properties. Finally, compound 4f was subjected to an in vivo pharmacokinetic study through two different routes of administration showing excellent oral bioavailability. This research represents compound 4f as a promising candidate against renal cell carcinoma.

Design and synthesis of novel isatin-based derivatives targeting cell cycle checkpoint pathways as potential anticancer agents

In recent years, cell cycle and checkpoint pathways regulation are offering new therapeutic approaches against cancer. Isatin, is a well exploited scaffold in the anticancer domain. Accordingly, the current work describes the design and synthesis of two series of (Z)-3-substituted-2-(((E/Z)-5-substituted-2-oxo-1-substituted-indolin-3-ylidene)hydrazinylidene)-thiazolidin-4-ones, 4(a-s) and (E/Z)-1-substituted-3-(((Z)-3-substituted-4-methylthiazol-2(3H)-ylidene)hydrazineylidene)-5-substituted-indolin-2-ones, 5(a-s). The structures of the synthesized molecules were confirmed by spectral and elemental methods of analyses. Pure diastereomers were further identified with 1H-1H-NOESY and confirmed with X-ray crystallography. The target compounds were tested in vitro for their cytotoxicity against three human epithelial cell lines, liver (HepG2), breast (MCF-7), and colon (HT-29) in addition to the diploid human normal cells (WI-38) compared to doxorubicin as a reference drug. Variable cytotoxic effects (IC50 3.29–100 ?μmol) were reported on the three cancer cell lines with pronounced selectivity compared to the normal one WI-38. The potency of the most active compounds, 4o, 4s, 5e, 5f, 5l, 5m and 5o (IC50 3.29–9.92 ?μmol), in both series associated with the (Z) configurations of N = thiazolidin/ene or one, however, the configuration of the N = isatin moiety seemed to be of no importance to the activity. The tested compounds were grouped for their possible mechanism of action into 4 categories. Compound 4o with no apparent effect on all genes examined. Compounds 4s and 5o affected all genes investigated and seem to have multiple cellular targets; induced the expression of p53 and caspases, and downregulated that of CDK1. Compounds 5l and 5m directly elevated the expression of initiator and effector caspases without going through p53 pathway. Finally, compounds 5e and 5f elevated the expression of p53 and inhibited CDK1. Compounds 4s, 5e, 5f, 5l, 5m, and 5o caused a significant elevation in the activity of cleaved caspase 3 as well. Docking studies on CDK1 revealed that the active molecules bind to the tested enzyme by the same manner of the co-crystallized ligands and the isatin-thiazoldinone/ene scaffold is essential for binding of these molecules.

Synthesis, DNA/protein binding, molecular docking, DNA cleavage and in vitro anticancer activity of nickel(ii) bis(thiosemicarbazone) complexes

A series of N-substituted isatin thiosemicarbazone ligands (L1-L5) and their nickel(ii) complexes [Ni(L)2] (1-5) were synthesized and characterized by elemental analyses and UV-Visible, FT-IR, 1H & 13C NMR, and mass spectr

THIOSEMICARBAZONES WITH MDR1 - INVERSE ACTIVITY

Disclosed herein are drug compounds that have MDR-inverse activity and thus are effective against multidrug-resistant cells. Exemplary compounds disclosed herein have the structure;Formula (I). Examples of the disclosed compounds have been found to have,

Synthesis and structure-activity evaluation of isatin-β- thiosemicarbazones with improved selective activity toward multidrug-resistant cells expressing P-glycoprotein

Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transport