The assembly and stability of FtsZ protofilaments have been shown to play critical roles in bacterial cytokinesis. Recent evidence suggests that FtsZ may be considered as an important antibacterial drug target. Curcumin, a dietary polyphenolic compound, has been shown to have a potent antibacterial activity against a number of pathogenic bacteria including Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus. We found that curcumin induced filamentation in the Bacillus subtilis 168, suggesting that it inhibits bacterial cytokinesis. Further, curcumin strongly inhibited the formation of the cytokinetic Z-ring in B. subtilis 168 without detectably affecting the segregation and organization of the nucleoids. Since the assembly dynamics of FtsZ protofilaments plays a major role in the formation and functioning of the Z-ring, we analysed the effects of curcumin on the assembly of FtsZ protofilaments. Curcumin inhibited the assembly of FtsZ protofilaments and also increased the GTPase activity of FtsZ. Electron microscopic analysis showed that curcumin reduced the bundling of FtsZ protofilaments in vitro. Further, curcumin was found to bind to FtsZ in vitro with a dissociation constant of 7.3±1.8 μM and the agent also perturbed the secondary structure of FtsZ. The results indicate that the perturbation of the GTPase activity of FtsZ assembly is lethal to bacteria and suggest that curcumin inhibits bacterial cell proliferation by inhibiting the assembly dynamics of FtsZ in the Z-ring.

Magnetic nanoparticles of γ-Mn_xFe_2–xO₃ (0 ≤ x ≤ 1.3) have been synthesized successfully using a single step process wherein the respective inorganic salts were thermally decomposed in ethylene glycol at 200 °C. Single phase formation is evident in the as prepared dried samples without any further treatment. XRD line broadening along with TEM suggest that the particle size is below 30 nm. Both the magnetic and XRD data support the substitution of Mn³⁺ ions at the tetrahedral site of γ-Fe₂O₃. Improved magnetization value (78 emu g^–1) is obtained for the sample with x = 0.2 compared to one with x = 0 (62 emu g^–1) if measured at 20 kOe. Aqueous suspensions of the sample with x = 0.2 were prepared using a polymer, Acrypol 934, with an aim to examine the possible use of these suspensions in the magnetic hyperthermia treatment of cancer. These suspensions were found to be biocompatible at concentration as high as 3.75 mg mL^–1 of culture media. Hyperthermia induced by the application of an AC magnetic field in the presence of the above suspension caused HeLa cell death. The cell death was found to be proportional to the quantity of the particles and the duration of application of the AC magnetic field. Following hyperthermia treatment, cells showed varying degrees of membrane blebbing with significant disruption of the actin and tubulin cytoskeletons. The apparent disruption of the actin and microtubule cytoskeletons of cells might be responsible for the death of cells following hyperthermia treatment. These observations suggest that the suspension of these particles may be evaluated for magnetic hyperthermia treatment of cancer.

The pathological aggregation of tau is a common feature of most of the neuronal disorders including frontotemporal dementia, Parkinson’s disease, and Alzheimer’s disease. The inhibition of tau aggregation is considered to be one of the important stra

The antifungal drug griseofulvin inhibits mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule (MT) function. Griseofulvin also blocks cell-cycle progression at G ₂ /M and induces apoptosis in human tumor cell lines. Despite extensive study, the mechanism by which the drug inhibits mitosis in human cells remains unclear. Here, we analyzed the ability of griseofulvin to inhibit cell proliferation and mitosis and to affect MT polymerization and organization in HeLa cells together with its ability to affect MT polymerization and dynamic instability in vitro . Griseofulvin inhibited cell-cycle progression at prometaphase/anaphase of mitosis in parallel with its ability to inhibit cell proliferation. At its mitotic IC ₅₀ of 20 μM, spindles in blocked cells displayed nearly normal quantities of MTs and MT organization similar to spindles blocked by more powerful MT-targeted drugs. Similar to previously published data, we found that very high concentrations of griseofulvin (>100 μM) were required to inhibit MT polymerization in vitro . However, much lower drug concentrations (1–20 μM) strongly suppressed the dynamic instability behavior of the MTs. We suggest that the primary mechanism by which griseofulvin inhibits mitosis in human cells is by suppressing spindle MT dynamics in a manner qualitatively similar to that of much more powerful antimitotic drugs, including the vinca alkaloids and the taxanes. In view of griseofulvin's lack of significant toxicity in humans, we further suggest that it could be useful as an adjuvant in combination with more powerful drugs for the treatment of cancer.