Mini Reviews in Medicinal Chemistry - Volume 18, Issue 12, 2018

Progress in the chemistry of cyclic enamino-nitriles based on the advanced synthetic methodologies is reported. Due to the recent accomplishment, it becomes possible to reactivate these molecules toward electrophiles, nucleophiles and as electron rich dienes in 2+3 dipolar additions and in 4+2 cycloadditions reactions. Synthesizing the poly functionalized 4H-pyrans and their fused derivatives is a fascinating field with a multitude of biological implications such as antitumor, cardiotonic, hepatoprotective, antihypertensive, antibronchitis, as well antifungal activity. This work was conducted with particular emphasis on reviewing the work done on the cyclic enamines since 1990 up till now in order to highlight in more details the synthetic pathways, interactions and the biological activities, Furthermore; we referred to the recent original data of our group contributions within this field.

Ornithine decarboxylase is the first enzyme in the polyamine biosynthetic pathway. It is the rate-limiting enzyme which is included during the change of ornithine to putrescine which is the first polyamine. Polyamines (putrescine, spermidine, spermine) are natural and synthetic compounds which contain two or more amino group. Polyamines are highly implicated in cellular functions such as cell growth & multiplication, DNA stabilization, gene transcription and translation, ion-channel activity, etc. Elevated levels of polyamines are found in highly proliferating tumor cells. Hence inhibition of this enzyme was found useful in cancer. α-DL-difluoromethylornithine(DFMO) (Eflornithine) an enzyme- activated irreversible inhibitor was the first of this type. However, its use as an anticancer agent did not continue for long due to various reasons. Polyamines have also been found to play an important role in other infectious microorganisms. Eflornithine is successfully used in diseases such as African sleeping sickness and is being researched against a number of tropical diseases. It is widely used against hirsutism in women. Various other product (putrescine) based analogs and transition state or PLP (cofactor) based analogs are being synthesized against diseases such as Leishmaniasis, Malaria and others discussed in the article.

Background: Natural aristolochia alkaloids have attracted the attention of both chemists and biologists from the stand point of their structural and pharmacological aspects. Many of the compounds isolated in this group are potent tumor inhibitors. These are divided into nitrophenanthrinic acid, phenanthrene lactams and isoquinoline alkaloids. A number of structure-activity studies have been performed on aristolochia alkaloids. Of particular interest is the molecule with the β-D-glucoside moiety that has similarity to the clinical anticancer agent daunomycin. Objective: The anticancer activity of aristololactam-β-D-glucoside has been thought to be due to its DNA and RNA binding activities among other actions. In this article we focus on the physicochemical property of this alkaloid and the structural and functional aspects of its binding to different nucleic acid and protein structures. Methods: This review highlights a large number of biophysical studies employing various analytical techniques like absorbance, fluorescence, circular dichroism, thermal melting, viscosity, IR study, isothermal calorimetry and differential scanning calorimetry. Result: The detailed binding mechanism in terms of the structural and thermodynamic aspects at the molecular level has been discussed. Conclusion: This review enables to assess the high potential of developing aristololactam-β-Dglucoside and related alkaloids as therapeutic agents.

Background: Alzheimer's disease (AD) is one of the most devastating diseases worldwide. The current drugs for AD can only ameliorate the symptoms rather than reverse or prevent the progress of AD. On the other hand, blood-brain barrier (BBB), as a natural barrier, significantly impedes drug delivery from the blood circulation into the brain. Nanomedicine can be a safe, effective and promising approach to treat AD. Objective: This review summarizes the recent nanomedicine research in this area, including the use of liposomes and nanoparticles (NPs), to provide new approach for targeted treatment of AD. Method: Collecting and referring to the related literature in recent 10 years, via searching MeSH Terms “Alzheimer's disease; nanomedicine; nanoparticle; amyloid β peptide; tau protein; autophagy”. Results: Nanomedicines show superiority over conventional anti-AD drugs as a potential weapon against AD by the five proposed mechanisms: many unfavorable pharmaceutical properties of conventional anti-AD drugs maybe greatly overcome by nanomedicine; nanomedicines trigger efficient production of high-titer anti-Aβ antibodies following controlled release of antigens by them; some apolipoprotein- based nanomedicines could preferably bind to Aβ and increase the elimination of Aβ; nanomedicine-induced autophagy could be facilitated to increase the elimination of Aβ; nanomedicineinduced inhibition of tau aggregation. Conclusion: Therefore, nanomedicine-mediated drug therapy is promising in the treatment of AD.

The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.

Background: The 3,4-diyne substituted isocoumarins have been designed, synthesized and explored as potential anti-proliferative agents. Method: Ultrasound assisted synthesis of these compounds was carried out by using a three-step method involving (i) Pd/C-Cu catalyzed cross-coupling between the methyl 2-iodobenzoate and buta- 1,3-diynylbenzene followed by (ii) I2-mediated electrophilic cyclization of the resultant 2-(alk-1- ynyl)benzoate ester and (iii) subsequent alkynylation of 4-iodo-3-(phenylethynyl)-isocoumarin under Pd/C-Cu catalysis. Conclusion: The synthesized compounds showed promising growth inhibition when tested against MDA-MB 231 and K562 cancer cell lines.