Bacteriocins: perspective for the development of novel anticancer drugs

Antimicrobial peptides (AMPs) from prokaryotic source also known as bacteriocins are ribosomally synthesized by bacteria belonging to different eubacterial taxonomic branches. Most of these AMPs are low molecular weight cationic membrane active peptides that disrupt membrane by forming pores in target cell membranes resulting in cell death. While these peptides known to exhibit broad-spectrum antimicrobial activity, including antibacterial and antifungal, they displayed minimal cytotoxicity to the host cells. Their antimicrobial efficacy has been demonstrated in vivo using diverse animal infection models. Therefore, we have discussed some of the promising peptides for their ability towards potential therapeutic applications. Further, some of these bacteriocins have also been reported to exhibit significant biological activity against various types of cancer cells in different experimental studies. In fact, differential cytotoxicity towards cancer cells as compared to normal cells by certain bacteriocins directs for a much focused research to utilize these compounds as novel therapeutic agents. In this review, bacteriocins that demonstrated antitumor activity against diverse cancer cell lines have been discussed emphasizing their biochemical features, selectivity against extra targets and molecular mechanisms of action.

     

The development of new anticancer drugs

World Journal of Microbiology and Biotechnology -     

Scheduling of anticancer drugs

Many cancer patients are treated with a combination of anticancer drugs. Here, we discuss the importance of drug scheduling and the need for studies that investigate the optimal timing of the various anticancer drugs. Positron emission tomography (PET) using radiolabeled anticancer drugs could be an important tool for those studies.     

Pyrrolizines: Promising scaffolds for anticancer drugs

Pyrrolizine derivatives constitute a class of heterocyclic compounds which can serve as promising scaffolds for anticancer drugs. The unique antitumor properties of mitomycin C inspired chemists to develop different pyrrolizine systems and assess their potential antitumor activities against a wide variety of cancer types. Here we review the different classes of pyrrolizines that possess anticancer potency, with an emphasis on their structure activity relationships, in an effort to pave the way for further development in this promising area of research.     

Ligand-targeted liposomal anticancer drugs

Antibody or ligand-mediated targeting of liposomal anticancer drugs to antigens expressed selectively or over-expressed on tumor cells is increasingly being recognized as an effective strategy for increasing the therapeutic indices of anticancer drugs. This review summarizes some recent advances in the field of ligand-targeted liposomes (LTLs) for the delivery of anticancer drugs. New approaches used in the design and optimization of LTLs is discussed and the advantages and potential problems associated with their therapeutic applications are described. New technologies are widening the spectrum of ligands available for targeting and are allowing choices to be made regarding affinity, internalization and size. The time is rapidly approaching where we will see translation of anticancer drugs entrapped in LTLs to the clinic.     

Cancer chemotherapy: identifying novel anticancer drugs.

There are now around 60 cytotoxic drugs licensed for use in cancer therapy in the United Kingdom. For certain malignancies such as childhood cancers, haematological malignancies, and germ cell tumours chemotherapy has been pivotal to the substantial improvement in therapeutic outcome achieved over the past 10 years. In contrast, improvements in the systemic management of adult solid tumours have been less dramatic. There is a clear and urgent need for new, more effective drugs for lung, breast, and colorectal malignancies. This paper examines the processes in identifying, developing, and evaluating new drugs with anticancer activity.     

Nanocarriers for anticancer drugs: Challenges and perspectives

Cancer is the second most common cause of death globally, surpassed only by cardiovascular disease. One of the hallmarks of cancer is uncontrolled cell division and resistance to cell death. Multiple approaches have been developed to tackle this disease, including surgery, radiotherapy and chemotherapy. Although chemotherapy is used primarily to control cell division and induce cell death, some cancer cells are able to resist apoptosis and develop tolerance to these drugs. The side effects of chemotherapy are often overwhelming, and patients can experience more adverse effects than benefits. Furthermore, the bioavailability and stability of drugs used for chemotherapy are crucial issues that must be addressed, and there is therefore a high demand for a reliable delivery system that ensures fast and accurate targeting of treatment. In this review, we discuss the different types of nanocarriers, their properties and recent advances in formulations, with respect to relevant advantages and disadvantages of each.     

Therapeutic aptamers: developmental potential as anticancer drugs

Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]     

Novel benzyl-substituted molybdocene anticancer drugs

From the reaction of 6-(p-methoxyphenyl) fulvene (1a), 6-(3,4-dimethoxyphenyl) fulvene (1b) and 6-(3,4,5-trimethoxyphenyl) fulvene (1c) with LiBEt₃H, lithiated cyclopentadienide intermediates (2a-c) were synthesised. These intermediates were then transmetallated to molybdocene using MoCl₄ (synthesized in situ) to yield the benzyl-substituted molybdocenes bis-[(p-methoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3a), bis-[(3,4-dimethoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3b), and bis-[(3,4,5-trimethoxybenzyl)cyclopentadienyl] molybdenum (IV) dichloride (3c). The molybdocene 3a was characterised by single crystal X-ray diffraction. All three molybdocenes had their cytotoxicity investigated through MTT based preliminary in vitro testing on the human renal cell line Caki-1 in order to determine their IC50 values and compare them with the corresponding titanocene and vanadocene dichloride derivatives. Molybdocenes 3b-c were found to have the same IC50 values of 290 μM, while 3a yielded a value of 84 μM, respectively     

Cyclophosphamide and related anticancer drugs

This article presents an overview of the methods of bioanalysis of oxazaphosphorines, in particular, cyclophosphamide, ifosfamide, and trofosfamide as well as their metabolites. The metabolism of oxazaphosphorines is complex and leads to a large variety of metabolites and therefore the spectrum of methods used is relatively broad. The various methods used are shown in a table and the particularly important assays are described.     

Electron-transfer activated metal-based anticancer drugs

Platinum(II)-based anticancer drugs play an essential role in the clinic today, and a number of coordination compounds with other metals are in current development as promising antitumor drugs. Probably the most prominent non-platinum metal-based drugs are those of ruthenium. Various strategies have been applied for the design of novel drugs with an improved toxicological profile, and one of them involves the preparation of metal complexes in inert high oxidation states [e.g. Pt(IV), Ru(III)]. Three platinum(IV) and two ruthenium(III) drugs have already reached clinical trials. Ideally, hypoxia-selective drugs are delivered to the target environment without prior reduction or major transformation via substitution reactions at the metal center. A (selective) reduction has been proposed to activate the prodrugs by formation of active species, which react with the target more readily and lead ultimately to apoptosis. Investigations on the electrochemical behavior of platinum(IV) and ruthenium(III) cytotoxins and the establishment of preliminary structure-property relationships are therefore of current importance. Herein, we present recent results in the field of metal-centered electron-transfer activated Ru(III), Pt(IV) and Co(III) drugs with regard to design and targeting strategies, prediction of redox potentials in aqueous medium, labilization and enhanced reactivity with potential biological targets upon reduction, and correlations between electrochemical parameters and anticancer activity.