In HIV-infected macrophages, newly formed progeny virus particles accumulate in intracellular plasma membrane-connected compartments (IPMCs). Although the virus is usually seen in these compartments, it is unclear whether HIV assembly is specifically targeted to IPMCs or whether some viruses may also form at the cell surface but are not detected, as particles budding from the latter site will be released into the medium. To investigate the fidelity of HIV-1 targeting to IPMCs compared to the cell surface directly, we generated mutants defective in recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) proteins required for virus scission. For mutants unable to bind the ESCRT-I component Tsg101, HIV release was inhibited and light and electron microscopy revealed that budding was arrested. When expressed in human monocyte-derived macrophages (MDM), these mutants formed budding-arrested, immature particles at their assembly sites, allowing us to capture virtually all of the virus budding events. A detailed morphological analysis of the distribution of the arrested viruses by immunofluorescence staining and confocal microscopy, and by electron microscopy, demonstrated that HIV assembly in MDMs is targeted primarily to IPMCs, with fewer than 5 % of budding events seen at the cell surface. Morphometric analysis of the relative membrane areas at the cell surface and IPMCs confirmed a large enrichment of virus assembly events in IPMCs. Serial block-face scanning electron microscopy of macrophages infected with a budding-defective HIV mutant revealed high-resolution 3D views of the complex organisation of IPMCs, with in excess of 15,000 associated HIV budding sites, and multiple connections between IPMCs and the cell surface. Using detailed quantitative analysis, we demonstrate that HIV assembly in MDMs is specifically targeted to IPMCs. Furthermore, 3D analysis shows, for the first time, the detailed ultrastructure of an IPMC within a large cell volume, at a resolution that allowed identification of individual virus assembly events, and potential portals through which virus may be released during cell-cell transfer. These studies provide new insights to the organisation of the HIV assembly compartments in macrophages, and show how HIV particles accumulating in these protected sites may function as a virus reservoir.

Plants continue to provide unlimited pharmacologically active compounds that can treat various illnesses, including cancer. The Solanaceae family, besides providing economically important food plants, such as potatoes and tomatoes, has been exploited extensively in folk medicine, as it provides an array of bioactive compounds. Many studies have demonstrated the anticancer potency of some of the compounds, but the corresponding molecular targets are not well defined. However, advances in molecular cell biology and in silico modelling have made it possible to dissect some of the underlying mechanisms. By reviewing the literature over the last five years, we provide an update on anticancer mechanisms associated with phytochemicals isolated from species in the Solanaceae plant family. These mechanisms are conveniently grouped into cell cycle arrest, transcription regulation, modulation of autophagy, inhibition of signalling pathways, suppression of metabolic enzymes, and membrane disruption. The majority of the bioactive compounds exert their antiproliferative effects by inhibiting diverse signalling pathways, as well as arresting the cell cycle. Furthermore, some of the phytochemicals are effective against more than one cancer type. Therefore, understanding these mechanisms provides paths for future formulation of novel anticancer drugs, as well as highlighting potential areas of research.

A new hexadentate 2-picolyl-polypyridyl-based ligand (4, 4'-(butane-1, 4-diylbis(oxy))bis(N, N-bis(pyridin-2-ylmethyl)aniline)) (2BUT) (1) and its corresponding Ru(II/III) complexes were synthesized and characterized, followed by assessment of their possible bioactive properties towards drug-resistant and non-drug-resistant bacteria. Spectroscopic characterization of the ligand was done using proton NMR, FTIR, and ESI-MS, which showed that the ligand was successfully synthesized. The Ru(II/III) complexes were characterized by FTIR, UV/Vis, elemental analysis, proton NMR, ESI-MS, and magnetic susceptibility studies. The analysis of ESI-MS data of the complexes showed that they were successfully synthesized. Empirical formulae derived from elemental analysis of the complexes also indicated successful synthesis and relative purity of the complexes. The important functional groups of the ligands could be observed after complexation using FTIR. Magnetic susceptibility data and electronic spectra indicated that both complexes adopt a low spin configuration. The disc diffusion assay was used to test the compounds for antibiotic activity on two bacteria species and their drug-resistant counterparts. The compounds displayed antibiotic activity towards the two non-drug-resistant bacteria. As for the drug-resistant organisms, only [Ru₂(2BUT)(DMF)₂(DPA)₂](BH₄)₄3 and 2, 2-dipyridylamine inhibited the growth of MRSA. Gel electrophoresis DNA cleavage studies showed that the ligands had no DNA cleaving properties while all the complexes denatured the bacterial DNA. Therefore, the complexes may have DNA nuclease activity towards the bacterial genomic material.

A new polypyridyl ligand 4‐(4‐nitrophenoxy)‐N,N‐bis (pyridin‐2‐ylmethyl)aniline (L1) and its three ruthenium (II/III) complexes, [Ru (Cl)₃L1] (C1), [Ru(L1)₂]Cl (C2), and [RuCl (dpa)L1] (C3) where dpa = 2,2‐dipyridylamine, have been successfully synthesized and characterized using Fourier‐transform infrared spectroscopy (FTIR), elemental analysis, proton nuclear magnetic resonance (¹H NMR), high‐resolution electrospray ionization mass spectrometry (HR‐ESI‐MS), thermal analysis (thermogravimetric analysis [TGA] and differential scanning calorimetry [DSC]), UV/Vis absorption, and magnetic susceptibility. The structures of the ligand and the complexes were optimized, and the structural characteristics were determined by density functional theory (DFT) using the B3LYP‐GD3/6‐311G++(d,p) method. Optimized FTIR vibrational frequencies and ¹H NMR chemical shifts agreed well with the corresponding experimental FTIR and ¹H NMR data. In vitro cytotoxicity of the ligand and the complexes were evaluated against the MCF‐7 breast cancer cell line. Ligand L1 was the most potent with an IC₅₀ of 38.45 μM, followed by C2 with an IC₅₀ of 45.23 μM. However, the ligand and the complexes showed low antiproliferative activity compared to cisplatin, which had an IC₅₀ of 9.67 μM. To predict the reactivity trend of L1 and the complexes, frontier molecular orbital (FMO) analysis was performed. The FMO energy gap (Eg = E_LUMO − E_HOMO) for C2 was found to be 1.675 eV, which was the lowest among all the complexes or L1. In addition, molecular docking studies were carried out so as to predict the binding capacity of L1 and the complexes to estrogen receptor alpha (ER‐α). The results showed that C2 has the most negative binding energy score (−9.63 kcal/mol), which indicates more stable adducts with the key amino acid residues at the active sites of ER‐α. Furthermore, C2 displayed the lowest inhibition constant (K_i) of 0.09 μM compared to all the complexes or L1. These results are very promising and show that the novel complex C2 may help in the development of anticancer drugs.

A series of ester and ether bridged compounds bearing the nitro and amino moieties were synthesized and characterized inorder to assess their ability to potentially serve as antibacterial agents against drug resistant bacteria. All the compounds were obtained at considerable yields while characterization techniques confirmed their succesful synthesis. Furthermore, their antimicrobial assesments showed that all the compounds exhibited antibacterial activity against the Gram-negative bacterial strains, both Klebsiella pneumoniae and its drug resistant counterpart. On the contrary they were poorly active against S. aureus and MRSA. According to the MIC data all the compounds showed activity of 0.22 to 0.24 mM towards MDR-K. pneumonieae. As for K. pneumoniae, the nitro derivatives L1 and L4 showed significantly higher MIC of 0.23 and 0.26 mM respectivelly while the amino derivatives L2 and L3 were more active, with MIC values of 0.16 mM. Finally, the time kill kinetics study showed that L2 and L3 were bacteriostatic while L1 and L4 were bactericidal towards K. pneumoniae. However, all the compounds were bactericidal towards MDR- K. pneumoniae.