synthesis and evaluation of dimethyl tin 4-cyclohexyl thiosemicarbazone as a novel antitumor age

Aim: To develop a rationally designed new organotin compound namely dimethyl tin 4-cyclohexyl thiosemicarbazone (D4-t) and evaluate its putative antitumor activity. Methods: Starting from 4-cyclohexyl thiosemicarbazone, a three step synthetic procedure was followed to obtain the title compound. In vivo lymphocyte activation property of the compound at three different doses was assayed by measuring the blastogenesis. Concanavalin A (ConA) was used as standard mitogen for murine T cells stimulation in vivo. Also, the synthesis of DNA by the activated lymphocytes was measured after injecting the D4-t. The lymphocyte activation property and antitumor efficacy of D4-twere assessed inSarcoma-180 (S-180) bearing mice. The organization of lymphoid cells was studied in the histological preparations ofspleen and mesenteric lymph node. Tumor neutralization assay (Winn assay) was conducted to examine whether immune responses were associated with the manifestation of antitumor efficacies of this compound in S-180 in vivo. The DNA synthesis inhibitory effect of the compound in S-180 cells was studied in vitro, and was found significant (P < 0.001). Results: Different doses of the new compound caused differential response of blastogenesis and DNA synthesis. In comparison to ConA, the title compound showed a good number of blast cells at its optimum dose of 5 mg/kg. It caused maximum synthesis of DNA by the lymphoid cells. In histological preparations, the gradual transformation of lymphocytes into blasts was observed without any visible toxicity. Winn assay revealed that 5 mg/kg of D4-t was able to reduce tumor mass without severe toxicity. This organotin compound also inhibits the synthesis of DNA in S-180 tumor cells in comparison to Platin10 and ConA. Conclusion: The title compound has the lymphocyte activation property and stimulates immune response of the lymphoid cells, which in turn express the antitumor activity without any significant toxicity. Results indicate promising therapeutic potential of D4-t

Architecture and self-assembly of clostridium sporogenes and clostridium botulinum spore surfaces illustrate a general protective strategy across spore formers

Spores, the infectious agents of many Firmicutes, are remarkably resilient cell forms. Even distant relatives can have similar spore architectures although some display unique features; they all incorporate protective proteinaceous envelopes. We previously found that Bacillus spores can achieve these protective properties through extensive disulfide cross-linking of self-assembled arrays of cysteine-rich proteins. We predicted that this could be a mechanism employed by spore formers in general, even those from other genera. Here, we tested this by revealing in nanometer detail how the outer envelope (exosporium) in Clostridium sporogenes (surrogate for C. botulinum group I), and in other clostridial relatives, forms a hexagonally symmetric semipermeable array. A cysteine-rich protein, CsxA, when expressed in Escherichia coli, self-assembles into a highly thermally stable structure identical to that of the native exosporium. Like the exosporium, CsxA arrays require harsh “reducing” conditions for disassembly. We conclude that in vivo, CsxA self-organizes into a highly resilient, disulfide cross-linked array decorated with additional protein appendages enveloping the forespore. This pattern is remarkably similar to that in Bacillus spores, despite a lack of protein homology. In both cases, intracellular disulfide formation is favored by the high lattice symmetry. We have identified cysteine-rich proteins in many distantly related spore formers and propose that they may adopt a similar strategy for intracellular assembly of robust protective structures

The Chiral Phase Transition in Dissipative Dynamics

Numerical simulations of the chiral phase transition in the (3+1)dimensional O(4)-model are presented. The evolutions of the chiral field follow purely dissipative dynamics, starting from random chirally symmetric initial configurations down to the true vacuum with spontaneously broken symmetry. The model stabilizes topological textures which are formed together with domains of disoriented chiral condensate (DCC) during the roll-down phase. The classically evolving field acts as source for the emission of pions and $\sigma$ mesons. The exponents of power laws for the growth of angular correlations and for emission rates are extracted. Fluctuations in the abundance ratios for neutral and charged pions are compared with those for uncorrelated sources as potential signature for the chiral phase transition after heavy-ion collisions. It is found that the presence of stabilizing textures (baryons and antibaryons) prevents sufficiently rapid growth of DCC-domain size, so observability of anomalous tails in the abundance ratios is unlikely. However, the transient formation of growing DCC domains causes sizable broadening of the distributions as compared to the statistical widths of generic sources.Comment: 28 pages, 8 figure

Chemical, electrochemical and structural studies of some cis-dioxomolybdenum(VI) complexes of two tridentate ONS chelating ligands

Several cis-dioxomolybdenum complexes of two tridentate ONS chelating ligands H2L1 and H2L2 ( obtained by condensation of S-benzyl and S-methyl dithiocarbazates with 2-hydroxyacetophenone) have been prepared and characterized. Complexes 1 and 2 are found to be of the form MoO2 (CH3OH)L-1.CH3OH and MoO2L, respectively, (where L2-=dianion of H2L1 and H2L2). The sixth coordination site of the complexes acts as a binding site for various neutral monodentate Lewis bases, B, forming complexes 3 - 10 of the type MoO2LB (where B=gamma-picoline, imidazole, thiophene, THF). The complexes were characterized by elemental analyses, various spectroscopic techniques, ( UV-Vis, IR and H-1 NMR), measurement of magnetic susceptibility at room temperature, molar conductivity in solution and by cyclic voltammetry. Two of the complexes MoO2(CH3OH)L-1.CH3OH (1) and MoO2L1(imz) (5) were structurally characterized by single crystal X-ray diffraction. Oxo abstruction reactions of 1 and 5 led to formation of oxomolybdenum(IV) complex of the MoOL type