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

Background: Urinary calculi can be caused by a variety of reasons, such as metabolic abnormalities, urinary tract infection and obstruction. Certain medications can induce urinary stone disease. Ceftriaxone, a third generation cephalosporin with broad spectrum antibiotic activity, primarily eliminated by the kidneys, has now been widely used for treatment of infection. It has been long considered safe, especially in children. However, more and more cases about ceftriaxone induced nephrolithiasis as a rare side effect have been reported. Conclusion: This complication generally resolves spontaneously with cessation of the drug. Severe nephrolithiasis can cause post renal acute renal failure (PARF). There is limited information about how this complication develops, though high doses and extended treatment periods are generally considered to be responsible. Understanding the mechanisms would help the doctors to be aware of this rare complication and respond with proper treatment. The primary goal of this review is to discuss the possible mechanisms based on the most recent literatures.

Objective: Animal associated-microbes are miroorganisms living inside animal hosts during some parts of their life. In view of the special environment, it is considered that the unique microbes might be the producer of new compounds with diversity biological activities. Conclusion: This review summarizes new findings (mainly described since 2011) concerning the characteristics of various natural products that can be extracted from animal associated-microbes, highlighting that animal related microorganisms represent an underexplored reservoir for the discovery of molecules with unique scaffolds and promising biological activities.

Objective: The present review article presented a detailed account of the design strategies and the structure activity relationship of different derivatives apart from the nitrogen containing ring. These scaffolds play an important part in the drug discovery which showed anticancer activity against different human cancer cell lines through apoptosis, cell cycle arrest, inhibiting kinases, angiogenesis, disruption of cell migration, modulation of nuclear receptor responsiveness and others. Naphthalenes amides/amidines, furan, podophyllotoxin, platinum compounds, steroids, and urea, which forms the core part or along with other N-heterocyclic rings are enclosed. Some of these compounds e.g. podophyllotoxin and platinum based drugs displayed anticancer activity at nanomolar range. Various substitutions from the earlier and latest information are prerequisite in the drug synthesis process. Conclusion: The review focused on the recent development of these derivatives, design and anticancer properties, thus providing with the most profound knowledge for the development of targeted based anticancer drugs.

Background: Atranorin, a compound with the depside structure, is one of the most common lichen secondary metabolites, characteristic for numerous lichen families but rarely found in some mosses and higher plants. Over the years various biological properties of atranorin were examined. Objective: This review summarizes the studies on atranorin, focusing on a number of biological activities in different fields. The literature describes anti-inflammatory, analgesic, as well as wound healing, antibacterial, antifungal, cytotoxic, antioxidant, antiviral, and immunomodulatory activities of the depside. Furthermore, lack of toxicity of atranorin was confirmed in the animals' in vivo assays. Conclusion: In conclusion, atranorin seems to be an interesting lichen substance, which needs to be investigated in more detail in order to allow further applications, e.g. in pharmacy, medicine or cosmetology.

Background: Botanical drugs contain plant extracts, which are complex mixtures of compounds. As with conventional drugs, it is necessary to validate their efficacy and safety through preclinical and clinical studies. However, pharmacokinetic studies for active constituents or characteristic markers in botanical drugs are rare. Objective: The objective of this review was to investigate the global state of the art in pharmacokinetic studies of active ingredients present in plant extracts and botanical drugs. A review of pharmacokinetics studies of chemical constituents of plant extracts and botanical drugs was performed, with a total of 135 studies published between January 2004 and February 2015 available in recognized scientific databases. Botanical preparations were mainly found in the form of aqueous extracts of roots and rhizomes. The most widely studied species was Salvia miltiorrhiza Bunge, and the compound most frequently used as a pharmacokinetic marker was berberine. Conclusion: Most studies were performed using the Sprague Dawley rat model, and the preparations were mainly administered orally in a single dose. Quantification of plasma concentrations of pharmacokinetic markers was performed mainly by liquid-liquid extraction, followed by high performance liquid chromatography coupled to mass spectrometry detector. In conclusion, in recent years there has been an increasing interest among researchers worldwide in the study of pharmacokinetics of bioactive compounds in botanical drugs and plant extracts, especially those from the Traditional Chinese Medicine.

Background: Acetylcholinesterase is a serine hydrolase that terminates the action of the neurotransmitter acetylcholine by hydrolyzing it into acetic acid and choline. Objective: The enzyme, containing an ellipsoidal structure, possesses three binding sites such as active site (with catalytic anionic and esteratic subsites), aromatic gorge and peripheral anionic site, where the inhibiting compounds interact. The acetylcholinesterase inhibitors bind to the enzyme and interfere with the breakdown of acetylcholine, leading to the deposition of acetylcholine in the nerve synapses and causing disrupted neurotransmission. Based on this principle of action, many therapeutic drugs for the treatment of different diseases, pesticides and chemical warfare agents have been synthesized targeting the actylcholinesterase. Conclusion: The present review summarizes the current knowledge about acetylcholinesterase, its structure, function and biosynthesis, its inhibitors, and mode of action of inhibitors on it. Besides, the review also presents an overview about the resistance mechanism that the organisms develop due to the over-application of acetylcholinesterase inhibitors.

Objective: Dioscorea opposita Thunb is the famous food and traditional medicine in China and it was rich in polysaccharides. Polysaccharides of Dioscorea Opposita Thunb possess immunoregulatory activity, free radical scavenging activity and anti-diabetic activity. A novel polysaccharide- iron(III) complex (CYPIC) was synthesized by using crude polysaccharide extracted from Dioscorea opposita Thunb. The component, structure, morphology and molecular weights of CYPIC were analysed, and the anti-anemia, acute toxicity and nonspecific immune regulating activities of CYPIC were assayed. The results showed that CYPIC could increase red blood cell count (RBC), hemoglobin (Hb), hematocrit (HCT), thymus and spleen index of mice with iron deficiency anemia (IDA). Although the structure and deeper mechanisms of CYPIC should be further studied, CYPIC has the potential to be used as an iron supplement for the treatment of iron deficiency anemia. Conclusion: The large scale industrial production was suggested due to the simple preparation processing of CYPIC.