Tuberculosis (TB) is an infectious disease caused by the bacterium, Mycobacterium tuberculosis (Mtb). The last surveys conducted by the World Health Organization (WHO) have described TB as the infectious disease responsible for the highest number of deaths worldwide. Furthermore, an increasing number of multidrug-resistant (MDR) and extensively-drug resistant (XDR) strains have complicated the scenario. In this regard, various N-oxide derivatives, such as furoxan, benzofuroxan, and quinoxaline 1,4-di-N-oxide, have been previously described as promising scaffolds with a potential to be explored as novel antitubercular drugs. Herein, 22 new N-oxide-containing compounds were synthesized followed by in vitro evaluation of their antitubercular potential against Mtb. Moreover, their safety and primary mechanism of action were also explored. The compounds demonstrated MIC₉₀ values ranging from 0.40 to 62 μM. Among the different heterocyclic compounds containing N-oxide, the benzofuroxan derivative 8 was found to be the most promising compound, with MIC₉₀ values of 1.10 and 6.62 μM against active and non-replicating Mtb, respectively. Cytotoxicity tests using MRC–5 cell line demonstrated an IC₅₀ value of 519.2 μM. Compound 8 was also active against monoresistant strains. Microarray-based initial studies on the mechanism of action revealed an upregulation of a number of transcripts encoding proteins belonging to both small and large subunits of the ribosome, suggesting that compound 8 blocked the process of translation. Altogether, these results indicated benzofuroxan derivative 8 to be a promising lead compound for the development of a novel chemical class of antitubercular drugs.

Prostatitis describes a combination of infectious diseases (acute and chronic bacterial prostatitis), chronic pelvic pain syndrome (CPPS) or asymptomatic prostatitis Most men with “chronic prostatitis” have chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by pelvic pain. The etiology of this syndrome is not fully known, the evaluation has been controversial and treatment is, unfortunately, frequently unsuccessful. Focused multimodal therapy appears to be more successful than empiric monotherapy. In that sense, it is important to know how nanoparticles will function in an animal model. The present paper reviews promising methods to capture prostate targeting.

Antibiotic resistance is an emerging disease and a real problem of health. Resistance of Gram negative bacteria such as Acinetobacter baumannii and Escherichia coli to conventional antibiotics lead to therapeutic failure and require new antibiotherapies. The use of the iron transport systems is one of the most promising strategies to overcome this resistance phenomenon. These specific routes of entry, essential for the survival of the microorganisms, allow ferric siderophore complexes to carry iron within the bacteria.

These systems allow the introduction of antibacterial agents (conjugates antibiotic-siderophore) or toxic complexes (gallium complexes) into the bacteria to kill them. Rhodotorulic acid (RA) is a siderophore transported by TonBox dependant Fhu receptors. These kinds of receptors are expressed by Acinetobacter baumannii and Escherichia coli. RA is dioxopiperazine iron chélater with hydroxamate as iron ligands and two asymmetric centers (S,S configuration). This spatial orientation is essential for the Fhu receptors recognition.

We have previously reported the asymmetric synthesis of 3-substituted 2-oxopiperazines. Herein, we present an original and a convergent strategy to synthesize RA and corresponding 3,6-disubstituted analogues. Siderophore-like test and measurement of the complexing strength of these compounds will be carried out.

The influenza (flu) virus infection induces an upexpression of tlr3, tlr7, tlr8, nfκb1, nfκbiα, nos2, xdh and other genes in mice lung. The nos2 and xdh upexpression causes overproduction of free radicals that lead to lung tissue damage. The upexpression of nfκb1, nfκbiα genes induce incorrect regulation of NF-κB. that regulates expression of the immune, inflammation genes and takes part in flu viral replication. The oligoribonucleotides-D-mannitol complexes (ORNs-D-M) possess antiviral activity against the flu virus in vitro and in vivo. One of mechanisms of the ORNs-D-M anti-influenza activity is direct virucidal action by blocking hemagglutinin–glycan interactions and inhibiting neuraminidase activity of flu virus. However other mechanisms of the ORNs-D-M anti-influenza activity have to be studied.

Current research was aimed at study of the ORNs-D-M effects on expression of the tlr3, tlr7, tlr8, nfkbia, nfnb1 nos2, xdh genes in mice lung under flu virus infection. To achieve this goal we applied a two-step RT-PCR assay. In mice lung after 48 h flu infection it was detected the overexpression of all investigated genes compared to the healthy ones. The ORNs-D-M injection for prevention reduced the mRNA level of tlr3, tlr7, tlr8, nfkbia, nfnb1 nos2, xdh expression by 65, 77, 76, 70, 63, 48, 32 % respectively vs the virus-infected mice. And the ORNs-D-M injection for treatment reduced the mRNA level of tlr3, tlr7, tlr8, nfkbia, nfnb1 nos2, xdh expression by 28, 17, 22, 40, 52, 41, 38 % respectively vs the virus-infected mice.

Our results show that the expression of all investigated genes is modulated by the ORNs-D-M after injection for prevention and treatment of the flu virus infection in vivo. It allows us to assume that by inhibiting the expression of tlr3, tlr7, tlr8, the ORNs-D-M impair the upregulation of nos2, xdh, nfkbia, nfkb1 induced by flu virus.

Combretastatin A-4(CA-4), a group of polyhydroxylated stilbenes isolated from the bark of the South African tree Combretum Caffrum, is a highly effective natural tubulin-binding molecule affecting microtubule dynamics by binding to the colchicines site. Its water soluble phosphate ester (CA-4P) is under evaluation in phase 3 trials for treatment of anaplastic thyroid cancer and in phase 2 trials for non-small cell lung cancer and platinum-resistant ovarian cancer, thus stimulating significant interest in a variety of combretastatin A-4 analogues. Unfortunately, a problem have limited their use as therapeutic agents. The cis configuration is biologically active, with the trans form showing significantly inactive. The active cis double bond in CA-4 is readily converted to the more stable trans isomer during storage or metabolism by heat, light, and protic media , resulting in a dramatic decrease in antitumor activity. Thus, it is necessary to design and discover novel cis configuration inhibitors based on CA-4.