Anti-Infective Agents - Volume 13, Issue 1, 2015

In recent times, bee venom (BV) from honey bee (Apis mellifera L.) has become the focus of interest as a form of alternative and preventive medicine for the treatment of a number of clinical cases such as arthritis, rheumatism, pain, cancer and a vast range of other conditions. BV contains several biochemically and pharmacologically active substances. Some of these compounds are well studied and their mechanisms of action established, despite the fact that few are undergoing clinical trials. Scientists are now performing intensive research work especially human clinical trials to improve the potential use of BV and its chemical constituents as the next drugs generation in the treatment of chronic disorders. Nevertheless, the dual effect of some bee venom components is also important in the design of future therapeutic goals. This paper gives recent evidences on the chemical and biological properties of the major components of bee venom, their underlying molecular action mechanism, and reasons of its consideration as a promising alternative medicine.

Propolis is identified as natural resource with effective biological and pharmacological activities. Here, we will discuss the plant sources, chemical composition, biological activities and toxicity of different types of propolis. Propolis is considered as a natural remedy against resistant microorganisms with a promising usage in the near future, but further studies should be conducted to investigate its therapeutic role.

Infectious diseases represent an important cause of mortality which motivated the pharmaceutical companies to develop new antimicrobial drugs in recent constant years, especially due to the constant emergence of microorganisms resistant to conventional antimicrobials. Nature has provided many things for humankind over the years, including the tools for the first attempts at therapeutic intervention. Api-products, recognized in traditional and modern medicine as active agents in some biological processes, have been used since ancient times. Their botanical origin is matters of great interest worldwide since the floral source of bee products plays an important role on their biological properties, as it could determine their antimicrobial activities.

Honey and other bee products have been subjected to laboratory and clinical investigations over the past few decades, the most significant discovery being their antibacterial activity. The emergence of antibiotic-resistant strains of bacteria has made the current use of antibiotic therapy problematic, resulting in earlier remedies being reassessed. Honey, propolis, royal jelly and bee venom, all exhibit strong antibacterial activity. Even antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) have been found to be as sensitive to honey as the antibiotic sensitive strains of the same species. The main problems in using bee products for medical purposes involve dosage and safety. The increased availability of licensed medical products containing bee products means that clinical use will probably grow and further evidence will become available. Use of such products in professional treatment centers should be limited to those which are safe and that exhibit proven antibacterial activities.

Honey has been shown to contain glucose oxidase, which produces gluconic acid and hydrogen peroxide from glucose. Dilution of honey results in a significant increase in the activity of this molecule. Inhibine, an antibacterial substance previously described in honey, has been identified as hydrogen peroxide, which is manufactured at inhibine assay by the natural glucose oxidase in honey. Inhibine levels have been shown to be directly associated with hydrogen peroxide production.

Royal jelly (RJ) is a unique secretion that is produced by the mandibular and hypopharyngeal glands of worker bees and used globally for its unique health benefits. It consists mainly of water, proteins, fatty acids, minerals, carbohydrates, vitamins, and other components. RJ as a raw and purified product has been evaluated for its bioactivity in in-vitro, animal and clinical studies and one of the most notable findings was its antimicrobial activity. Although there are many types of antibiotics that can inhibit the growth of pathogenic bacteria, antibiotic-resistant strains have emerged, leading to a search for alternative methods through the re-examination of past remedies. Certain components in RJ have shown antimicrobial effects against a wide range of microbes, including bacteria, viruses, yeast, and fungi. Trans-10- hydroxy-2-decenoic acid, Royalisin, and Jelleines are the main antimicrobial biaoctives obtained from RJ, and they have significant antibacterial potential. This review is on the antimicrobial effects of RJ and their potential use in medical and other applications.

A series of isatin imines incorporated with 4-sustituted phenyl 2-amino thiazole was synthesized on the basis of molecular hybridization drug design principle. The structures of the derivatives were confirmed by IR, ¹HNMR and Mass analyses. The titled derivatives were screened against M.tuberculosis strain H37RVusing alamar blue susceptibility test. Compound 3-{[4-(4- hydroxyphenyl)-1, 3-thiazol-2-yl] imino}-1, 3-dihydro-2H-indol-2-one (IIT2) was found to be most active with a MIC of 6.25μg/ml. Preclinical evaluation of the compounds was ascertained by in silico toxicity and ADME parameters. It has been concluded that the hydrogen contributing groups present in the phenyl system of the titled scaffold favours the activity ratio.

In this study 26 novel benzimidazole compounds bearing alkyl chain as linker at N-1 position were synthesized and evaluated to investigate their possible anti-HIV and antimicrobial activities. Structures of the synthesized compounds were elucidated by spectral data. HIV-1 RT inhibitory activity was evaluated by using HIV-1 RT RNA-dependent DNA polymerase activity assay. Among these derivatives, compounds 43, 45, 50 and 51 were found to have reasonable HIV-1 RT inhibitory activity while the rest exhibited weak activity in comparison to the standard efavirenz. On the other hand, most of the test compounds were found to be significantly effective against gram positive bacteria (Staphylococcus aureus and Bacillus subtilis) and some gram-negative bacterial strains (Escherichia coli, Salmonella typhi, Klebsiella pneumoniae and Pseudomonas aeruginosa), among which compounds 37, 43, 45, 50 and 51 surfaced out as the most effective antibacterials but less effective than the standard ciprofloxacin. Compounds 33, 41 and 47 also showed significant activity against almost all the bacterial strains while all other compounds showed moderate activity towards all the bacterial strains. In case of fungal strains like Candida albicans and Aspergillus niger, almost all the compounds were found to exhibit potency comparable or more than that of standard drug fluconazole except for the compounds 34, 39, 42, 47 and 48 which exhibited moderate to good activity against both the fungal strains. A structure activity relationship (SAR) as well as virtual ADME and toxicity prediction were carried out and a connection between activities, electronic, physicochemical properties and toxicity levels of the target compounds was determined.

Polymers exhibiting anti–microbial properties constitute an important class of bioactive polymers whose properties can be easily tuned by simple polymer analogous reactions. Two series of new polymers were synthesized from 4–Vinyl pyridine, which was polymerized and quaternized in situ by using alkyl bromides of varying alkyl chain length. The well–characterized polymers were evaluated for their anti–microbial activity against a gram (–) bacterium (Citrobacter freundii) and fungus (Mucor circinelloides), and penicillin and fluconazole were the respective references. Polymer that exhibited the best activity was subjected to anion metathesis reactions as Br– was replaced with –OH, SO4 2, HSO3 –, NO3 – or CH3COO– to generate another series of new polymers. All the polymers exhibited strong antimicrobial activity against both the microbes studied. Polymer having butyl alkyl chain and –OH as counter ion exhibited the strongest activity with minimum inhibitory concentration of 60.0 μg/mL and 250 μg/mL, respectively, against the bacterium and fungus studied.

The antibacterial and antibiofilm activities of several amphiphillic tetracationic calixarenes with different functional groups were evaluated. Our results demonstrate the clear dependence of antibacterial activity from the alkyl chain length on the lower rim of calixarene. Tetrapropoxycalixarenes have 10-50 times higher antibacterial activity than tetraoctyl calixarenes with same cationic residues on the upper rim. At the same time, one of the tetrapropoxycalixarenes shows high inhibitory activity against Staphylococcus aureus biofilms. Therefore, the alkyl chain length is an important characteristic that can be used for further antibacterial agent design.