Mini Reviews in Medicinal Chemistry - Volume 13, Issue 7, 2013

The present paper discusses models of 5-HT1A and 5-HT2A receptors, developed by conformational analysis and 3D-QSAR methods. Hypotheses concerning the ligand-5-HT7 receptor interaction were complemented by models constructed on the basis of the receptor's structure. Various pharmacophore concepts are supported by structures of exemplary ligands and groups of compounds, derived from chain polycyclic arylpiperazines, used for models generations.

Chalcones are a group of plant-derived polyphenolic compounds belonging to the flavonoids family and possess a wide variety of cytoprotective and modulatory functions. In this research we tried to review the anticancer effect of chalcones derivatives and to evaluate new QSARs which will help in the understanding of the role of chalcones and of their analogs on cancer. Simultaneously a comparative study will be presented. Our QSAR results reveal that: 1) the clog P (hydrophobicity/hydrophilicity) parameter plays an important part in three QSAR relationships (linear model), 2) the steric factors such as molar volume MgVol, molar refractivity CMR or the substituents molar refractivity MR (linear) are important. Electronic effects are comparatively unimportant. These results compared to our previous findings on the QSAR of anti-proliferative chalcones support primarily the role of bulk.

Hydrazide/hydrazone derivatives are of quite interest for medicinal chemists because of their vast spectrum of biological activity. Literature reports reveal that the hydrazide derivatives have been extensively studied for their biological profile during the past decade. The aim of the present work is to collect literature reports focusing the antimicrobial and anticancer study of different hydrazide/hydrazone derivatives carried out during the past decade which will serve as a valuable source of information for the researchers working in the field of antimicrobial and anticancer research.

α-Amino-α-halomethylketones are interesting scaffolds bearing (at least) two sequential electrophilic carbons that by interacting with the nucleophilic moieties of several enzymes, represent the ideal candidates for in vivo and in vitro inhibition studies. In this work a summary of their use as optimal inhibitors of physiologically relevant serine and cysteine proteases is given with a particular emphasis on recently established SAR studies. A brief survey of the most relevant synthetic processes for their obtainment and the importance they possess in synthetic medicinal chemistry is reported.

Chagas Disease (CD), a tropical parasitic disease caused by the flagellate protozoan Trypanosoma cruzi, accounts for the highest burden of parasitic diseases in the Western hemisphere. Current drug treatments for CD are highly toxic and often ineffective, particularly for the chronic stage of the disease, a fact that clearly emphasizes the importance of identification/validation of molecular targets for the development of new drugs to treat the disease. Here, we review in details the evidences that suggest the existence of specific receptors for platelet-activating factor (PAF) in T. cruzi, the role of PAF on the control of parasite differentiation and the potential of exploring these putative receptors as new targets for the chemotherapy of CD.

Inhibition of Histone deacetylases (HDACs) has been emerged as important approach to reverse aberrant epigenetic changes associated with various cancerous and non-cancerous diseases. The field of histone deacetylase inhibitors (HDIs) is moving into a new phase of development. The structure of histone deacetylases is well-established and the active sites have been well identified. Various drugs targeting this enzyme are in the pipeline for the treatment of different diseases. Since first-generation HDAC inhibitors proved their clinical fruitfulness and also second generation inhibitors are rationally designed with improved specificity, experts believe that this class will emerge in the treatment of various diseases. Considering these facts present review focuses on HDACs and developments of HDIs in the treatment of various diseases.

Among the plethora of heterocyclic nucleus discovered, the oxadiazoles have also been explored extensively. The oxadiazole structure has been demonstrated to bear important biological activities such as anti-cancer, antiinflammatory, anti-tuberculosis, anti-malarial and anti-schistosomiasis etc. The presence of oxadiazole motifs in diverse types of compounds proves its importance in the field of medicinal chemistry. This review is complementary to earlier reviews and covers recent updates of various pharmacological aspects of oxadiazoles. To help the reader better know the context for these approaches, a summary of various aspects of background of related topic is presented.

The HIV-1 viral infectivity factor (Vif), one of the six accessory proteins, is essential for viral replication and pathogenesis. Its main function is to form Vif-Cullin5-ElonginBC complex and then is able to ubiquitinate and degrade the human anti-viral factor APOBEC3G, which markedly enhances the virus infectivity. Delete Vif leads to the loss of the infectivity of HIV-1; therefore, Vif is a potentially new attractive target for therapeutic intervention in AIDS. This review describes the structure, function and especially inhibitors of HIV-1 Vif.

Malaria is an infectious disease causing almost one million deaths each year. There is an urgent need for discovery of new antimalarial compounds. Natural products have been the single most productive source of leads for the development of drugs, because of their great variety of chemical structures. This review covers studies on antimalarial natural products isolated from plants, published from January 2010 until April 2012. A total of 171 structures comprising alkaloids, terpenoids, phenolics and other metabolites are listed in this review, including information on their antiplasmodial and cytotoxic activity.

Resistant pathogenic microbial strains are emerging at a rate that far exceeds the pace of new anti-infective drug development. In order to combat resistance development, there is pressing need to develop novel class of antibiotics having different mechanism of action in comparison to existing antibiotics. Antimicrobial peptides (AMPs) have been identified as ubiquitous components of innate immune system and widely regarded as a potential source of future antibiotics owing to a remarkable set of advantageous properties ranging from broad spectrum of activity to low propensity of resistance development. However, AMPs present several drawbacks that strongly limit their clinical applicability as ideal drug candidates such as; poor bioavailability, potential immunogenicity and high production cost. Thus, to overcome the limitations of native peptides, peptidomimetic becomes an important and promising approach. The different research groups worldwide engaged in antimicrobial drug discovery over the past decade have paid tremendous effort to design peptidomimetics. This review will focus on recent approaches in design of antimicrobial peptidomimetics their structure–activity relationship studies, mode of action, selectivity & toxicity.