Background Recently various lactic acid bacteria (LAB) and their post-metabolites have shown many positive effects on human and animal welfare. They appear to be beneficial in different disorders and pathological conditions, including in a broad-spectrum of infectious diseases. Aim To estimate in vitro the anti-herpes simplex activity of 11 postbiotic samples (lysates or cell-free supernatants - CFS) produced during the fermentation of six candidate-probiotic Lactobacillus strains isolated from Bulgarian fermented milk products. Materials and methods In vitro protocols for assessment of different LAB samples on the Herpes simplex virus type 1 (HSV-1) replication, adsorption and virucidal effects were applied using MDBK cells. Results Four of the studied LAB samples expressed a statistically significant inhibition of the replication of HSV-1. The highest selective index (79.75) was calculated for the post-metabolites of Lactiplantibacillus plantarum , followed by a high molecular fraction of cell-derived fragments of Limosilactobacillus fermentum culture (S6) (SI = 34.63), CFS from late exponential L. plantarum (SI = 28.26) and neutralized CFS from L. fermentum (SI = 28.11). Pronounced virucidal activities of the postbiotics S1, S11 ( L. fermentum ), S3 ( L. plantarum ) and S6 ( L. fermentum ) were recorded, too. The inhibitory effect of the majority of the samples on the stage of adsorption of the virus to MDBK cells was remarkable. In addition, almost all of the postbiotics exerted a protective effect on healthy cells and significantly reduced viral yield at subsequent infection. Conclusion Pre-selected Lactobacillus strains demonstrated strain-specific effects against HSV-1. These postbiotics influence different stages of viral infection in cell cultures and their promising characteristics are currently evaluated.

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzothiazolone (26Z) exhibits the most potent cytotoxic activity (IC50 0.13 ± 0.01 µM) against EA.hy926 cells. 26Z not only inhibits vasculogenesis but also disrupts pre-existing vasculature. 26Z is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. 26Z also shows anti-proliferative activity in CA-4 resistant cells with the following IC50 values: HT-29 (0.008 ± 0.001 µM), MDA-MB-231 (1.35 ± 0.42 µM), and MCF-7 (2.42 ± 0.48 µM). Cell-cycle phase-specific experiments show that 26Z treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some 26Z-treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by 26Z has an exciting chemotherapeutic potential that merits further investigation.

Background: Histone deacetylase (HDAC) inhibitors are a new class of therapeutic compounds that show promising results in a series of preclinical and clinical anticancer studies. Hydroxamic acids belong to one of the most interesting classes of HDAC inhibitors. The member vorinostat (SAHA) was approved by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma. Methods: A series of eight novel hydroxamic acids containing 2-imidazolylphenyl(oxy/thio)alkanoic fragment designed to target histone deacetylase (HDAC) were synthesized in five steps from easily accessible 2(3H)-benzoxazolones and 2(3H)-benzthiazolones. The newly synthesized compounds were characterized by 1H, 13C NMR, and elemental analysis. Results: The structure-activity relationship was examined via linker length alternation and variation of the heteroatom (oxygen or sulfur) and chlorine substitution pattern of the starting materials. The compounds were tested for their cytotoxic activity against two human cancer cell lines (HT-29 and MDA-MB-231). Our data indicate that the compound 6.1d is active in the micromolar range with IC50 of 9.7 µM for MDA-MB-231 cells. DNA fragmentation analysis of the most active compounds confirmed that apoptosis could be one of the mechanisms involved in cell death. Conclusion: Taken together, the results revealed that 6d may become a promising lead compound for new anticancer drugs discovery.

Background: The accumulation of data on beneficial biological effects of probiotics and their metabolic products favors their potential use in the prevention and treatment of various malaises. Methods: Nine postmetabolites from Lactic acid bacteria (LAB) of human or dairy origin and their antiviral activity were studied using the cytopathic effect inhibition test. The virucidal capacity, their influence on the adsorption stage of Koi herpes virus (KHV) and their preventive role against subsequent viral challenge on intact Common carp brain (CCB) cells were also determined by titration assay. Residual viral infectivity in postmetabolites-treated samples was compared to mock-treated controls and Δlgs were calculated. Results: When administered during KHV replication, the microbial products isolated from Lactiplantibacillus plantarum showed remarkable activity with a selectivity index (SI) between 26.5 and 221.4, as those effects were dependent on the sample-virus incubation time. Postmetabolites from Lactobacillus gasseri and Lactiplantibacillus plantarum also demonstrated significant inhibition of KHV replication with SI of 24 and 16, respectively. The bioactive metabolites isolated from Limosilactobacillus fermentum had a minor effect on the viral replicative cycle. Compounds, produced during the fermentation by lactobacilli, grown on different nutritive media and collected at different time points, significantly inhibited extracellular KHV virions. All investigated postmetabolites remarkably blocked KHV attachment to the host cell (CCB), leading to a drop in viral titers by Δlg = 4.25–5.25, and exerted protective effects on CCB cells before they were subjected to viral infection. Conclusions: Our results open new horizons and promote LAB and their postbiotic products to be used in the prophylaxis and therapy of viral infections.