Mini Reviews in Medicinal Chemistry - Volume 17, Issue 16, 2017

Objective: Ionizing radiation has been shown to impact and possibly alter the normal structure and function of living cells and is dangerous for human health, especially when exposure occurs early in life. Additionally, radiation can interact with other dangerous substances in the same environment, such as phthalates. Phthalates are a group of multifunctional molecules used in a wide range of consumer products, as plasticizers to impart flexibility, durability and strength to otherwise rigid polyvinyl chloride. They are not chemically bound to polyvinyl chloride, and thus migrate into the environment with time and use, becoming ubiquitous environmental contaminants. Conclusion: There is a growing concern about the effect that exposure to ionizing radiation and phthalates can have on human health, and the biological effects of this cumulative exposure are particularly troubling in infants due to children's inherent sensitivity. Pediatric patients are exposed to numerous plastic medical devices and often require multiple radiologic examinations for their complex medical conditions. Risk assessment requires a more complete evaluation of the effects of simultaneous and cumulative exposure, especially in high-risk patients.

Background: One of the most studied anti-cancer compounds of the last several decades is the microtubule targeting agent and cis-stilbene, combretastatin A4 (CA4). Despite promising results at the pre-clinical level, future clinical use of CA4 as a monotherapy is in question due to metabolic vulnerability and conformational instability. Objective: Thus, medicinal chemists have focused on synthesizing derivatives with improved pharmokinetic profile. One common strategy has been the incorporation of the ethylene linker into a ring system, thus preventing the isomerization of CA4 into the virtually inactive trans-isomer. Although many structurally stable and potent analogues of CA4 have been designed and synthesized, several analogues have been discovered to possess anti-proliferative properties seemingly independent of microtubule targeting. The presence of such analogues suggests that CA4 may also possess nonmicrotubule targets, which reveals the necessity for future structure activity relationship studies and optimization of any non-microtubule targeting. Furthermore, analogues of CA4 not inhibiting microtubule polymerization can no longer be assumed to be inactive. Conclusion: Future clinical development of the CA4 pharmacophore requires that attention should be paid to abnormal CA4 analogues, which appear to retain cytotoxicity independent of canonical microtubule inhibition.

Objective: The spirooxindole heterocyclic scaffold is found in many natural products and has been identified as an important bioactive agent. Background: Over the past few decades, various spirooxindole-containing compounds have been reported to possess biological properties and hence found in the structure of many synthetic pharmaceuticals. This mini-review describes the most promising examples of this class of compounds possessing biological activity including anticancer, anti-inflammatory, and antimicrobial activities. Conclusion: The current review focuses on the biological activity of compounds containing the spirooxindole scaffold.

Background: This review looks into the herbs Gingko biloba, Polygala tenuifolia, and Lycii fructus for their widely studied neuroprotective properties. In particular, we investigated memory enhancing effect of these herbs, and their potential synergetic effect on memory with new data. Sixmonth treated mice demonstrated shorter escape latency in water maze and shorter arrival time in a consolidated memory task. Immunochemistry showed evident increase in superoxide dismutase activities in the prefrontal cortex, implying protection against free radicals during aging. Discrete increase of catecholaminergic neurons was found in the prefrontal cortex, hippocampus, corpus striatum, and midbrain, suggesting better memory and better control on mood and behavior. Necrotic cells in the brain decreased as indicated by immunocytochemistry of lactic dehydrogenase. Terminal deoxynucleotidyl transferase dUTP nick end labeling showed no apoptotic cells in most brain areas in high dose group. Biochemistry revealed increase of dopaminergic cells in treatment groups at prefrontal cortex, and in the hippocampus and cerebellum of the high dose group. Most 6-month groups showed increase of serotonin in all three areas. For the high dose group, GABA increased in the hippocampus but not prefrontal cortex, which would help induce sleep at night. Protein kinase C increased in most groups at prefrontal cortex, hippocampus and cerebellum, signifying increase of possible signal transduction pathways for memory or other nervous activations. Conclusion: Our results intimate that the interaction of the three herbs exerts beneficial effects on memory, associated cognitive function, and necrosis. Future investigations based on the present data shall aid development of clinically relevant medication.

Background and Objective: Bacitracin was discovered and named after a 7 year old American girl, Margaret Tracey in 1943 as Bacillus was isolated from her wounds. Bacillus licheniformis is usually present in soil and bird feathers. This bacterium is most commonly present around back plumage and chest of birds. There are different types of bacitracin but the one most potent is Bacitracin A. Bacitracin induced proteins are localized in bacterial membrane. Production of antibiotic initially stopped, resumed by induction of bacitracin induced protein but after few mitotic divisions microbes reverted to their vulnerable state. Induction of protein ceases after 4th hour of stationary phase. Immobilization is necessary for economic, process convenience and stability of the cell. Moreover, immobilization increases the ability of the cell to produce product in high quantity. Conclusion: Maximum production of antibiotic was noted at pH 8 after 4 hours of incubation at various glucose concentrations in shake flask fermentation at 30°C when immobilized in polyacrylamide gel. Increase in antibiotic activity was also found with increase in use of cells. Efforts have been made to alter heterocyclic metal binding subunit of bacitracin by synthesizing heterocyclic building blocks that can be coupled to linear decapeptide and consequently cyclization by PCPTE biodomain of bacitracin. Derivatives of bacitracin showed antimicrobial activities indicating the possibility of overcoming existing limitations just by altering their heterocyclic subunit. Bioactivity and stability can be increased by modifying peptide backbone of compounds.

Background: On account of significant biological activities, quinoline derivatives have drawn more attention to the synthesis and biological activities in the search for new therapeutic agents. Several new synthetic approaches have been implemented to derive new molecules from quinoline and all the synthesized molecules showed effective anticancer activity. Method: Some molecules are synthesized using quinolones as precursor reactant, which is another effective product of quinoline, also showing significant activity against malignant tumors. The presence of nitrogen in it and its ability to bind with enzymes like gyrase, topoisomerase II and kinase have also proven it with antitumor activity. Conclusion: This review encapsulates the recent advances in the synthesis and anticancer activity of Quinoline derivatives.

Background: Microwave assisted modification of polymers has become an established technique for modifying the functionality of polymers. Microwave irradiation reduces reaction time as well as the use of toxic solvents with enhanced sensitivity and yields of quality products. Objective: In this review article instrumentation and basic principles of microwave activation have been discussed. Microwave assisted grafting of natural gums, characterization of grafted polymers and their toxicological parameters have also been listed. Pharmaceutical applications viz. drug release retardant, mucoahesion and tablet superdisintegrant potential of microwave assisted gums has also been discussed. Conclusion: An overview of microwave assisted extraction of plant based natural materials has also been presented.