Novel Piperazine Based Compounds Target Alzheimer's Disease Relevant Amyloid β42 and Tau Derived Peptide AcPHF6, and the Lead Molecule Increases Viability in the Flies Expressing Human Tau Protein.

Alzheimer's disease (AD) is the leading form of dementia in the United States and the world. The pathophysiology of AD is complex and multifaceted. Accumulation of senile plaques and neurofibrillary tangles (NFTs) are hallmarks of AD.

PROTAC'ing oncoproteins: targeted protein degradation for cancer therapy.

Molecularly targeted cancer therapies substantially improve patient outcomes, although the durability of their effectiveness can be limited. Resistance to these therapies is often related to adaptive changes in the target oncoprotein which reduce binding affinity. The arsenal of targeted cancer therapies, moreover, lacks coverage of several notorious oncoproteins with challenging features for inhibitor development.

Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.

The vast majority of cancer patients receive DNA-damaging drugs or ionizing radiation (IR) during their course of treatment, yet the efficacy of these therapies is tempered by DNA repair and DNA damage response (DDR) pathways. Aberrations in DNA repair and the DDR are observed in many cancer subtypes and can promote carcinogenesis, genomic instability, and ensuing resistance to current cancer therapy. Additionally, stalled or collapsed DNA replication forks present a unique challenge to the double-strand DNA break (DSB) repair system.

Novel aryl piperazines for alleviation of 'andropause' associated prostatic disorders and depression.

A series of seventeen piperazine derivatives have been synthesized and biologically evaluated for the management of andropause-associated prostatic disorders and depression. Five compounds 16, 19, 20, 21 and 22 significantly inhibited proliferation of androgen-sensitive LNCaP prostatic cell line with EC values of 12.4 μM, 15.

Ammonium salts of carbamodithioic acid as potent vaginal trichomonacides and fungicides.

Chemical attenuation of the reactive oxygen species (ROS)-sensitive anaerobes Trichomonas vaginalis, which is the most prevalent non-viral sexually transmitted infection, and two often coexisting vaginal infections, namely Candida albicans and Staphylococcus aureus, which are opportunistic reproductive tract infections, was attempted with novel ammonium salts of carbamodithioic acid through inhibition of free thiols. In vitro and in vivo efficacies of the designed compounds were evaluated as topical vaginal microbicides. Five compounds showed exceptional activity against drug-resistant and -susceptible strains with negligible toxicity to host (HeLa) cells in vitro in comparison with the standard vaginal microbicide nonoxynol-9 (N-9), without disturbing the normal vaginal flora (i.

Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-β from degradation and induce apoptosis in prostate cancer cells.

Purpose: To investigate apigenin (5,7,4-trihydroxyflavone), a dietary flavonoid with proteasome-inhibitory activity (desired for the management of multiple types of cancers), against FDA-approved anticancer proteasome inhibitor bortezomib in context to its effects on the tumor suppressor estrogen receptor-beta (ER-β) in prostate cancer cells.

Methods: Prostate cancer (PC-3) cells were treated with either apigenin or bortezomib, and proliferation inhibition was correlated with proteasomal biochemistry, ER-degradation and cell apoptosis.

Results: Apigenin specifically inhibited only chymotrypsin-like activity of proteasome without affecting trypsin and caspase-like activities, which was in contrast to the non-specific inhibition of all the three activities by bortezomib.

Exosomes: Emerging Players of Intercellular Communication in Tumor Microenvironment.

Seminal discoveries have established the role of complex tumor microenvironment (TME) in cancer progression; and later on also uncovered that vesiculation is an integral part of intercellular communication among various cell types in coordinating the tumor assembly in a dynamic manner. Exosomes are small membrane bound endosomal vesicles, which are classically known for their role in discarding cellular wastes; however, recent reports underlined their novel role in malignancy by their release from cells into the TME. Since then, the role of exosomes have been a subject of increasing interest, as exosome mediated intercellular communications offer a novel reciprocal relationship between cancer and stromal cells within the TME and modulate the fate and function of the recipient cells to finally shape the tumor progression.