Mini Reviews in Medicinal Chemistry - Volume 17, Issue 2, 2017

Technetium-99m (99mTc) is widely used as a radionuclide for labeling of biomolecules in nuclear medicine practice. 6-hydrazinopyridine-3-carboxylic acid namely HYNIC is one of the best bifunctional chelating agents for attachment of 99mTc to the biomolecules such as peptides and proteins. Since HYNIC can only occupy one or two coordination sites of 99mTc, co-ligands are needed to complete the coordination sphere of the technetium. Selection of co-ligands can be impressive on the stability, lipophilicity and biodistribution of 99mTc-HYNIC conjugated peptides. The aim of this review was to explain the chemical and biological effects of various co-ligands on characteristics of 99mTc-HYNIC conjugates for tumor or diseases imaging.

Neuropathic pain is originated from different alterations of the nervous system. The difficulty of treatment strongly impairs quality of life of affected people. It is associated with severe, chronic sensory disturbances characterized by spontaneous pain, increased responsiveness to painful stimuli and pain perceived in response to normally non-noxious stimuli. The underlying mechanisms are complex and involve both peripheral and central nervous components. The noradrenergic system plays a pivotal role in the control of pain since its widespread distribution in the “pain matrix” representing a valuable therapeutic target. This review focused on the α2 adrenoceptor subtype modulation as strategy for neuropathic pain relief. Drugs acting as direct α2 adrenoceptor agonists (clonidine and dexmedetomidine) were analyzed as well as the indirect α2 adrenoceptor modulators. The overview included norepinephrine reuptake inhibitors (reboxetine, maprotiline), serotonin/norepinephrine reuptake inhibitors (venlafaxine, milnacipran, amitriptyline, duloxetine, bicifadine) and the compounds characterized by a double pharmacodynamic mechanism combining the norepinephrine reuptake inhibition and the μ opioid agonist profile (tramadol and tapentadol). A summary of recent compounds was illustrated.

Hyperpigmentation is an abnormal darkening of the skin mostly derived from excessive melanin production. It is typical of skin disorders including melasma associated to pregnancy or age, freckles, sun freckles and photoaging, age spots, and actinic keratosis. These conditions can be uncomfortable for aesthetic reasons and specific depigmenting treatment is frequently requested. Tyrosinase (EC 1.14.18.1) is the rate-limiting enzyme of melanin synthesis and the main target of antihyperpigmentation remedies. Much interest is focused on compounds able to inhibit tyrosinase activity, particularly natural products, for which there is an increasing demand in the fields of cosmetics and pharmaceutical applications. This review concerns plants from the Moraceae family that have shown tyrosinase inhibition in vitro, including species from the genera Morus, Artocarpus, Maclura (Cudrania), Broussonetia, Milicia (Chlorophora), and Ficus. Compounds with remarkable tyrosinase inhibitory properties have been isolated from the wood and bark of different species, such as calchones, stilbenoids, flavonoids and diterpenes. Studies of structure-activity relationships have suggested that an unsubstituted resorcinol moiety is important for the acquirement of strong tyrosinase inhibition, but various exceptions have been reported. A few species, such as M. alba, A. heterophyllus, A. incisus, Maclura tricuspidata, and C. excelsa, have also shown inhibition of melanin biosynthesis on cultured melanoma cells. In addition, wood extract and the stilbene artocarpin from A. incisus have induced whitening effects on guinea pig skin, while an extract from A. lakoocha has hindered melanin formation in human volunteers. The complex of data indicates that Moraceae plants deserve attention for the development of natural and semi-synthetic tyrosinase inhibitors able to compete with, or outclass, currently available skin whitening drugs.

The increasing incidence of microbial resistance and newly emerging pathogens have become a serious challenge for public health. More and more efforts have been directed to the development of new antimicrobial agents with distinct mechanisms from the well-known classes of clinical drugs. The extensive clinical utilization of azole-based medicinal drugs has evoked numerous attentions, and their researches and developments have been a quite rapid developing and active highlight topic with an infinite space. Consideration of our researches on azole compounds and other literature in recent three years, this review scientifically reviewed the new progress of azole derivatives as antibacterial, antifungal, antitubercular and antiviral agents, including mono-nitrogen azoles (oxazoles, thiazoles and carbazoles), bis-nitrogen azoles (imidazoles, pyrazoles and benzimidazoles) and tri-nitrogen azoles (triazoles and benzotriazoles) as well as tetrazole derivatives. It was hoped that this review would be helpful for the design and development of highly efficient azole derivatives with high bioactivity and low toxicity.

Tuberculosis (TB) is highly infectious disease causing morbidity and death. Its causative organism is a contagious bacterium, Mycobacterium tuberculosis. The incidence of tuberculosis is increasing worldwide due to the emergence of drug resistance bacteria. The resistance is being developed in Mycobacterium tuberculosis against both the first line as well as the second line drugs used for the treatment. The tuberculosis control programme is being complicated and failed to get the desired impact due to the development of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis. So, there is a critical requirement to discover and produce newer anti-TB drugs with unique drug targets. Medicinal plants have been used for curing the diseases from ancient time. Medicinal plants are the novel sources for the production of alternate medicines for the treatment of TB caused by MDR and XDR strains. Plants produce a number of different kinds of secondary metabolites such as Alkaloids, Coumarins, Flavonoids, Polyphenols, Terpenoids, Quinines, etc. which have antimicrobial activity; thus may be useful in control of tuberculosis. These compounds do not contribute directly in growth and development but used by the plants for their defense. On the basis of various sources in the literature, about 72 phytochemicals constituents responsible for anti tubercular activity isolated from different plants have been explained along with their structure. Most effective isolated compounds from plants are plumbagin, maritinone, 3, 3’-biplumbagin, aloe emodin, epigallocatechin and umckalin. These phytochemicals are helpful for the treatment of MDR, XDR type of tuberculosis. This review describes an overview of the current synthetic medicines used for treatment of TB and the work carried out on anti tubercular plants along with their phytochemicals.