A newly synthesized thiosemicarbazide derivative trigger apoptosis rather than necroptosis on HEPG2 cell line.

Thiosemicarbazide derivatives have been the focus of scientists owing to their broad biological activities such as anticancer, antimicrobial, and anti-inflammatory. Herein, we designed and synthesized a new thiosemicarbazide derivative (TS-1) and evaluated its antiproliferative potential against the human hepatocellular carcinoma cell line (HEPG2) and human umbilical vein endothelial cell line (ECV-304). Also, it was aimed to investigate the necroptotic and apoptotic cell death effects of TS-1 in HEPG2 cells, and these effects were supported by molecular docking. The new synthesized compound structure was characterized using various spectroscopic methods such as FT-IR, 1 H-NMR, 13 C-NMR, and elemental analysis. The cytotoxic activity of the tested compound was measured by the MTT assay. Apoptotic and necroptotic properties of the TS-1 were evaluated by indirect immunoperoxidase method using antibodies against Ki-67, Bax, Bcl-2, caspase-3, caspase-8, caspase-9, RIP3, and RIPK1. Apoptotic and necroptotic effects of TS-1 were supported by molecular docking. Compound TS-1 was synthesized as a pure compound with a high yield. The effective value of TS-1 was 10 µM in HEPG2 cells. TS-1 did not show any cytotoxic effect on ECV-304. Caspase-3 and RIPK1 immunoreactivities were significantly increased in HEPG2 cells after being treated with TS-1. As the results of the molecular docking studies, the molecular docking showed that the TS-1 exhibits H-bond interaction with various significant amino acid residues in the active site of both RIPK1. It could be concluded that TS-1 could be a promising novel therapeutic agent by inducing apoptosis rather than necroptosis in HEPG2 cells.

Synthesis, characterization, and antimicrobial evaluation of some new hydrazinecarbothioamide, 1,2,4-triazole and 1,3,4-thiadiazole derivatives.

In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a-d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a-n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a-g). The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi.

2-[6-(4-Bromo-phen-yl)imidazo[2,1-b][1,3]thia-zol-3-yl]-N-[8-(4-hy-droxy-phen-yl)-2-methyl-3-oxo-1-thia-4-aza-spiro-[4.5]decan-4-yl]acetamide ethanol disolvate.

In the title compound, C(28)H(27)BrN(4)O(3)S(2)·2C(2)H(6)O, the cyclo-hexane ring adopts a chair conformation. The imidazo[2,1-b][1,3]thia-zole ring system is essentially planar with a dihedral angle of 1.1 (2)° between the thia-zole and imidazole rings. The mean plane of this ring system makes dihedral angles of 8.11 (16) and 79.43 (17)°, respectively, with the bromo- and hy-droxy-substituted benzene rings. In the 5-methyl-1,3-thia-zolidin-4-one group, the S atom, the methyl group and the ring C atoms bonded to them are disordered over two sets of sites with refined occupancies of 0.610 (19) and 0.390 (19). The crystal structure features N-H⋯O, O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds and C-H⋯π inter-actions. Furthermore, two weak π-π stacking inter-actions [centroid-centroid distances = 3.967 (3) and 3.892 (2) Å] are also observed.

Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

2-[6-(4-Chloro-phen-yl)imidazo[2,1-b][1,3]thia-zol-2-yl]-N'-[(E)-4-meth-oxy-benzyl-idene]acetohydrazide.

In the imidazo[2,1-b][1,3]thia-zole group of the title compound, C(21)H(17)ClN(4)O(2)S, the dihedral angle between the thia-zole and imidazole rings is 1.9 (2)°. The mean plane of this group makes dihedral angles of 5.5 (2) and 39.9 (2)° with the benzene rings of the chloro-phenyl and meth-oxy-phenyl groups, respectively. The dihedral angle between these two benzene rings is 34.4 (2)°. In the crystal, mol-ecules are connected to each other by inter-molecular N-H⋯O hydrogen bonds along the b axis, generating a C(4) chain. Weak C-H⋯π inter-actions also occur.

Synthesis and antimicrobial activity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b]thiazole moiety.

A series of 4-alkyl/aryl-2,4-dihydro-5-((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-3H-1,2,4-triazole-3-thiones (3a-i) and 2-alkyl/arylamino-5-((6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)-1,3,4-thiadiazoles (4a-c) were synthesized starting from 6-(4-bromophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide. The newly synthesized compounds were characterized by IR, (1)H NMR, mass and elemental analysis. All compounds were tested for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by the microbroth dilution technique. The compounds were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294). The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.

2-[(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino]-1-methyl-2-oxoethyl pyrrolidine-1-carbodithio-ate.

In the title compound, C(19)H(24)N(4)O(2)S(2), inversion-related mol-ecules are linked together to form a dimer by N-H⋯O and C-H⋯O hydrogen bonds, generating two R(2) (1)(6) rings and one R(2) (2)(10) ring motif. An inter-molecular C-H⋯O hydrogen bond connects the dimers to each other. An intra-molecular C-H⋯O inter-action occurs. In the pyrrolidine ring, the two C atoms of the ring not bonded to the N atom displays positional disorder with site-occupation factors of 0.630 (18) and 0.370 (18).

N-(3-Oxo-1-thia-4-aza-spiro-[4.5]dec-4-yl)-6-phenyl-imidazo[2,1-b][1,3]thia-zole-3-acetamide hemihydrate.

The title compound, C(21)H(22)N(4)O(2)S(2)·0.5H(2)O, crystallizes with two mol-ecules in the asymmetric unit. The dihedral angles between the phenyl and imidazothiazole ring systems are 19.16 (9) and 21.37 (9)°. In the imidazothiazole ring systems, the cyclohexane rings adopt chair conformations, while the thiazole rings have distorted envelope conformations. The two mol-ecules are stabilized by intra-molecular N-H⋯O, O-H⋯O and C-H⋯S inter-actions and the crystal structure is stabilized by inter-molecular N-H⋯O, O-H⋯O, C-H⋯O and C-H⋯N inter-actions.

Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives.

A series of arylidenehydrazides (3a-3i) were synthesized from [6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The structures of new compounds were determined by analytical and spectral (IR, (1)H NMR, (13)C NMR, EIMS) methods. The synthesized compounds (3a-3i) were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. Compounds 3a-3c, 3h and 3i which passed the criteria for activity in this assay were scheduled automatically for evaluation against the full panel of 60 human tumour cell lines at a minimum of five concentrations at 10-fold dilutions. Compounds 3c demonstrated the most marked effects on a prostate cancer cell line (PC-3, log(10)GI(50) value<-8.00).