Synthesis of Novel α-l-Arabinopyranosides of β-Lactams with Potential Antimicrobial Activity

Synthetic routes toward the synthesis of some novel 1-(2,3,4-tri-O-acetyl-α-l-arabinopyranosyl)-azetidin-2-ones are described. Antimicrobial screening of three selected compounds revealed their activity against Bacillus subtilis and Escherichia coli.     

Selective Synthesis and Structure of 6-Arylvinyl-2- and 4-Glucosyl-1,2,4-triazines of Expected Interesting Biological Activity

Abstract

The 6-β-arylvinyl-2- and 4-glucosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones were synthesized with high selectivity using the recently developed amino protecting group strategy. The structure of these new glucosides was established chemically and spectroscopically. Also, some interesting chemical transformations and rearrangements were observed.     

Assessment of Soluble and Biomass K in Culture Medium Is a Reliable Tool for Estimation of K Releasing Efficiency of Bacteria

Abstract

Assessing the amount of released K from minerals in bacterial liquid culture is the main process for screening and isolation of efficient potassium releasing bacteria (KRB). This study was aimed to determine the amount of released K in solution phase or supernatant (SK) as well as microbial biomass K (MBK). Therefore, 20 different bacterial isolates belonging to the 10 bacterial genera (Beijerinckia, Klebsiella, Azotobacter, Pseudomonas, Agrobacterium, Rhizobium, Sphingomonas, Citrobacter, Microbacterium, and Achromobacter) were individually used to inoculate Aleksandrov medium in presence of biotite or muscovite. Our results from in-vitro experiments revealed that the MBK (K in pellet) is more important than in SK. Although some genera such as Azotobacter and Citrobacter released more SK (16?mg/l from biotite and 12.77?mg/l from muscovite, respectively), the Klebsiella isolates with the highest MBK could release an average of 90?mg/l total K. This study indicated that the assimilated K in microbial cells is the main part of K dissolution from minerals. Due to the fast turnover of nutrients in bacterial biomass, it can be concluded that both SK and MBK could be available for plants. It seems that the finding of this research should be considered in the isolation of KRB.

Highlights

• This study reports, assessment of soluble and biomass K in the culture medium is a reliable tool for estimation of K releasing efficiency of bacteria

• Our results from in vitro experiments revealed that the assimilated K in microbial cells is the main part of K dissolved from minerals.

• Although some genera such as Azotobacter released more K in solution phase, the Klebsiella isolates with the highest biomass K could release more total K

     

Synthesis,cyclooxygenase inhibitory effects,and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and -2-alkylsulfonyl-1H-imidazole derivatives

A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively.     

Phase II Study of Concurrent Capecitabine and External Beam Radiotherapy for Pain Control of Bone Metastases of Breast Cancer Origin

Background

Pain from bone metastases of breast cancer origin is treated with localized radiation. Modulating doses and schedules has shown little efficacy in improving results. Given the synergistic therapeutic effect reported for combined systemic chemotherapy with local radiation in anal, rectal, and head and neck malignancies, we sought to evaluate the tolerability and efficacy of combined capecitabine and radiation for palliation of pain due to bone metastases from breast cancer.

Methodology/Principal Findings

Twenty-nine women with painful bone metastases from breast cancer were treated with external beam radiation in 10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral capecitabine 700 mg/m² twice daily was administered throughout radiation therapy. Rates of complete response, defined as a score of 0 on a 10-point pain scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2 weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates of partial response, defined as a reduction of at least 2 points in pain score without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%. The overall response rate (complete and partial) at 12 weeks was 86%. Side effects were of mild intensity (grade I or II) and included nausea (38% of patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot syndrome (7%).

Conclusions/Significance

External beam radiation with concurrent capecitabine is safe and tolerable for the treatment of pain from bone metastases of breast cancer origin. The overall and complete response rates in our study are unusually high compared to those reported for radiation alone. Further evaluation of this approach, in a randomized study, is warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01784393","term_id":"NCT01784393"}}NCT01784393{"type":"clinical-trial","attrs":{"text":"NCT01784393","term_id":"NCT01784393"}}NCT01784393     

The Chemical Diversity of Lantana camara: Analyses of Essential Oil Samples from Cuba,Nepal, and Yemen

The aerial parts of Lantana camara L. were collected from three different geographical locations: Artemisa (Cuba), Biratnagar (Nepal), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 39 L. camara essential oil compositions revealed eight major chemotypes: β‐caryophyllene, germacrene D, ar‐curcumene/zingiberene, γ‐curcumen‐15‐al/epi‐β‐bisabolol, (E)‐nerolidol, davanone, eugenol/alloaromadendrene, and carvone. The sample from Cuba falls into the group dominated by (E)‐nerolidol, the sample from Nepal is a davanone chemotype, and the sample from Yemen belongs to the β‐caryophyllene chemotype. The chemical composition of L. camara oil plays a role in the biological activity; the β‐caryophyllene and (E)‐nerolidol chemotypes showed antimicrobial and cytotoxic activities.     

Nanoformulation of curcumin protects HUVEC endothelial cells against ionizing radiation and suppresses their adhesion to monocytes: potential in prevention of radiation-induced atherosclerosis

Objectives

To investigated the potential of a novel dendrosomal nanoformulation of curcumin (DNC) in blocking radiation-induced changes in irradiated human umbilical vein endothelial cells (HUVECs), and their adhesion to human THP-1 monocytoid cells.

Results

Co⁶⁰ gamma rays reduced viability, raised the expression of adhesion molecules, ICAM-1, VCAM-1 and E-selectin (mRNA and protein), augmented the adhesion of THP-1 cells to HUVECs, activated NF-κB binding, increased the release of pro-inflammatory cytokines (IL-6, IL-8 and MCP-1) and induced oxidative damage (reduced glutathione declined, while 8-OHdG and TBARS increased). 5 µM DNC significantly inhibited these radiation-induced changes, activated the Nrf-2 pathway, and effectively suppressed THP-1 adhesion to HUVECs, implicating p38 MAPK signaling.

Conclusion

DNC treatment is a potential preventive method against inflammation and vascular damage from ionizing radiation.

     

Adjuvant chemotherapy with melatonin for targeting human cancers: A review

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.     

The roles of moonlight ribosomal proteins in the development of human cancers

“Moonlighting protein” is a term used to define a single protein with multiple functions and different activities that are not derived from gene fusions, multiple RNA splicing, or the proteolytic activity of promiscuous enzymes. Different proteinous constituents of ribosomes have been shown to have important moonlighting extra-ribosomal functions. In this review, we introduce the impact of key moonlight ribosomal proteins and dependent signal transduction in the initiation and progression of various cancers. As a future perspective, the potential role of these moonlight ribosomal proteins in the diagnosis, prognosis, and development of novel strategies to improve the efficacy of therapies for human cancers has been suggested.     

Tumor microenvironment: Interactions and therapy

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.