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Structure and biological activities of synthetic peptides corresponding to human alpha-defensin HNP-1, AC1YC2RIPAC3IAGERRYGTC4IYQGRLWAFC5C6 with the S-S connectivities: C1-C6, C2-C4, C3-C5, and its variants with one, two and three disulfide bridges were investigated. Oxidation of synthetic, reduced HNP-1 yielded a peptide with S-S connectivities C1-C3, C2-C4 and C5-C6, and not with the S-S linkages as in naturally occurring HNP-1. Selective protection of cysteine sulfhydryls was necessary for the formation of S-S bridges as in native HNP-1. Likewise, oxidation of peptide encompassing the segment from C2 to C5, resulted in the S-S linkages C2-C3 and C4-C5 instead of the expected linkage C2-C4 and C3-C5. Antibacterial activities were observed for all peptides, irrespective of how the S-S bridges were linked. Linear peptides without S-S bridges were inactive. Circular dichroism (CD) spectra suggest that peptides constrained by one and two S-S bridges do not form rigid beta-sheet structures in an aqueous environment. The spectrum of HNP-1 in an aqueous environment suggests the presence of a beta-hairpin conformation. In the presence of lipid vesicles, the S-S constrained peptides tend to adopt a beta-structure. Although the S-S connectivities observed in HNP-1 may be necessary for other physiological activities, such as chemotaxis, they are clearly not essential for antibacterial activity.

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Docetaxel (DTX) is found to be very effective against glioma cell in vitro. However, in vivo passage of DTX through BBB is extremely difficult due to the physicochemical and pharmacological characteristics of the drug. No existing formulation is successful in this aspect. Hence, in this study, effort was made to send DTX through blood-brain barrier (BBB) to brain to treat diseases such as solid tumor of brain (glioma) by developing DTX-loaded nanoliposomes. Primarily drug-excipients interaction was evaluated by FTIR spectroscopy. The DTX-loaded nanoliposomes (L-DTX) were prepared by lipid layer hydration technique and characterized physicochemically. In vitro cellular uptake in C6 glioma cells was investigated. FTIR data show that the selected drug and excipients were chemically compatible. The unilamellar vesicle size was less than 50 nm with smooth surface. Drug released slowly from L-DTX in vitro in a sustained manner. The pharmacokinetic data shows more extended action of DTX from L-DTX in experimental rats than the free-drug and Taxotere Õ . DTX from L-DTX enhanced 100% drug concentration in brain as compared with Taxotere Õ in 4 h. Thus, nanoliposomes as vehicle may be an encouraging strategy to treat glioma with DTX.

Nowadays, novel pharmacies have been screened from plants. Among them are the peptides, which show multiple biotechnological activities. In this report, a small peptide (Ala-Trp-Lys-Leu-Phe-Asp-Asp-Gly-Val) with a molecular mass of 1,050 Da was purified from Cycas revoluta seeds by using reversed-phase liquid chromatography. This peptide shows clear deleterious effects against human epidermoid cancer (Hep2) and colon carcinoma cells (HCT15). It caused inhibition of cancer cell proliferation and further disruption of nucleosome structures, inducing apoptosis by direct DNA binding. A remarkable antibacterial activity was also observed in this same peptide. Nevertheless, no significant lysis of normal RBC cells was observed in the presence of peptide. Additionally, an acetylation at the N-termini portion is able to reduce both activities. Bioinformatics tools were also utilized for construction of a three-dimensional model showing a single amphipathic helix. Since in vitro binding studies show that the target of this peptide seems to be DNA, theoretical docking studies were also performed to better understand the interaction between peptide and nucleic acids and also to shed some light on the acetyl group role. Firstly, binding studies showed that affinity contacts basically occur due to electrostatic attraction. The complex peptide-ssDNA was clearly oriented by residues Ala(1), Lys(3), and Asp(6), which form several hydrogen bonds that are able to stabilize the complex. When acetyl was added, hydrogen bonds are broken, reducing the peptide affinity. In summary, it seems that information here provided could be used to design a novel derivative of this peptide which a clear therapeutic potential.

Background: Glucose level alters susceptibility of antifungal agents during chemotherapy in diabetes patients. Results: Glucose selectively interacts with antifungal agents, strongly affects azole drugs, and forms complexes by hydrogen bonding. Conclusion: It is important for researchers and pharmaceuticals to make new antibiograms for diabetes patients. Significance: Drug selection is important for controlling fungal infections in diabetes patients.Effects of glucose on the susceptibility of antifungal agents were investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents; voriconazole was the most affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interactions between antifungal agents with glucose molecules were investigated using isothermal titration calorimetry, Fourier transform infrared, and 1 H NMR. Glucose has a higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility of antifungal agents during chemotherapy. In addition to confirming the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the glucose. In vivo results also suggest that the physiologically relevant higher glucose level in the bloodstream of diabetes mellitus mice might interact with the available selective agents during antifungal therapy, thus decreasing glucose activity by complex formation. Thus, proper selection of drugs for diabetes mellitus patients is important to control infectious diseases. Among several emerging diseases, DM3 is considered one of the largest emerging threats to public health in the 21st century. From the medical profession to the general public, individuals are well aware that the greater frequency of metabolic disorders and morbimortality in diabetic patients are due to the hyperglycemia. Extra glucose in blood and urine provides an increased propensity to develop infections, and diabetes patients are especially prone to foot infections, yeast infections, urinary tract infections, and surgical site infections (1, 2). The prevalence of yeast infection is more common in patients with DM because of the higher density of candidal growth (3,4). Candida species are the part of the body's normal oral and intestinal flora, but infection becomes more severe in DM patients with higher levels of inflammation (5, 6). Antifungal medications, such as clotrimazole, nystatin, fluconazole, and ketoconazole, are very effective in controlling topical yeast infections. In the case of candidal infections in blood, the choices of drugs are intravenous fluconazole or echinocandin or amphotericin B (AmpB) (7,8). However, there is no such specific indication of the choice of drug for people suffering from DM. When a patient is suffering from DM and has a yeast infection, that patient is more likely to get other infections because the combinat...

A smart, ultrafast, light-responsive nanogel is a potential carrier for on-demand and immediate delivery of therapeutic agents. Here, a novel branched pentaerythritol poly­(caprolactone)-b-poly­(acrylic acid)-based smart, light-responsive nanogel has been fabricated by using ferric ion (Fe3+) as a cross-linker. The mentioned block copolymer has been synthesized by combining both the ring opening and atom transfer radical polymerization techniques. Branched structure of the polymer offers a minute amount (1.5 mol %) of Fe3+ sufficient for nanogel formation. The nanogel looks like a spherically shaped human brain holding the water molecule as like cerebrospinal fluid in the brain. The particle size of the nanogel has been tailored (between 30 and 450 nm) by separately varying both the molar concentration of Fe3+ and polymer chain length. The highly negative zeta potential (−46 mV) of the nanogel promotes its impressive colloidal stability and prolongs the circulation time in vivo. Nanogels securely hold the DOX molecules (maximum drug loading capacity: 26.2%). Exposure of light onto the nanogel (in the presence of lactic acid) produces immediate initiation of de-cross-linking followed by the release of DOX molecules (85.2% at 120 min). The nanogel shows significantly high uptake and acute toxicity against a cancerous cell line (C6 glioma) in vitro. Administration of the DOX-loaded nanogel on the C6 glioma rat model (in vivo) offered tremendous inhibition (∼91%) of tumor growth without any toxic side effects (confirmed by histopathology).