RSC Medicinal Chemistry Blog

Antimalarial drugs with increased in vitro activity have been developed by scientists in Portugal and the US. These novel drugs, called primacins, are active against two stages of malarial infection and are more active against liver parasites than the current clinical use drug, primaquine.

Mosquito-borne malaria is a highly infectious and potentially fatal disease that affects millions of people every year. When humans are bitten by a malaria-infected mosquito, they undergo a clinically silent liver-stage infection when thousands of malaria parasites (merozoites) are released into the bloodstream. Drugs that are active against liver parasites are rare and currently, primaquine is the only drug in clinical use. However, its use is hampered by low oral bioavailability and high hemotoxicity, making it unsuitable for pregnant women, children and the elderly.

The new primacins, developed by Paula Gomes from the University of Porto, Portugal, and co-workers combine primaquine with cinnamic acids, which are also known for their antimalarial activity. ‘This ‘‘covalent bitherapy’’ involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual activity into a single hybrid molecule,’ explains Gomes. ‘So far, none of the antimalarials reported in the literature combine these two antimalarial pharmacophores. Moreover, the chemistry underlying their preparation is simple and cheap, which is our constant concern when dealing with development of antimalarials, as malaria is mainly endemic to low income countries.’

Larry Walker, a professor in pharmacology at the University of Mississippi, US, agrees that the work is promising, but says that further experiments and animal testing are necessary. ‘What is new here is the finding that, using this liver stage parasite culture model, which is fairly new and very useful, they can show improved potency of these derivatives. This is really the most important feature of this study,’ he says. ‘However, it is important to keep in perspective what still needs to be done to have a real advance for this drug class. What is needed is to show that it improves activity in animal models; and more importantly, shows reduced hematological toxicity compared to primaquine.’

Gomes agrees that in vivo tests are the way forward: ‘The next step consists of establishing how active our compounds are in vivo, how are they absorbed, distributed, metabolised and eliminated,’ she says. ‘If the compounds are confirmed to be highly active in vivo, we’ll then step forward into the so-called pre-clinical assays.’

REFERENCES

1. Chemistry World story by Emma Eley

2. B Pérez et al, MedChemComm, 2012, DOI: 10.1039/c2md20113e

Insulin could be administered topically rather than by needles in the future

Scientists in Japan have developed a way to administer insulin to patients through the skin. Such a method avoids one of the problems associated with injections and oral administration in which a drug’s concentration is reduced as it passes through the digestive system. It would also be a more pleasant experience for patients.

Masahiro Goto from Kyushu University in Fukuoka and SO Pharmaceutical Corporation in Kobe, and colleagues, prepared a capsule loaded with insulin that is able to penetrate the skin with its cargo.

The team made their capsule by surrounding insulin molecules with proteins and coating the protein molecules with a hydrophobic surfactant to form protein–surfactant complexes. Then, they added oligo-arginine peptides as protein transduction domains and dispersed the complexes in oil – isopropyl myristate – which is known to have a permeation-enhancing effect. ‘The main function of this new system is to promote protein penetration through the hydrophobic stratum corneum [outermost layer of the skin],’ explains Goto.

The team tested their delivery vehicle on pig skin and found that the solid-in-oil dispersion delivered six times more insulin into the skin than an aqueous solution. The peptides further enhanced the concentration of insulin delivered through the skin.

‘Transcutaneous protein delivery is a difficult problem, the solution of which could enhance the quality of life for patients in need of protein therapeutics,’ says Paschalis Alexandridis from the chemical and biological engineering department at the University of Buffalo, US, whose work includes pharmaceutical formulations. He adds that Goto’s work demonstrates the versatility of solid-in-oil nanodispersions as a platform for enhanced transdermal delivery of protein therapeutics and vaccines.

Goto and his team say that in theory such dispersion could be used for any drug that is soluble in water and can form a water-in-oil emulsion. They hope to be able to produce a transdermal vaccine in the future.

Original story from Chemistry World, written by Jennifer Newton

The 2011 Journal Citation Reports ® (Thomson Reuters, 2012) have just been released, which showed:

Organic & Biomolecular Chemistry: 3.696

MedChemComm: 2.8         (Partial IF only, based on five issues)

Natural Product Reports: 9.79

The Cambridge Editorial Office would like to thank everyone involved for their hard work and dedication to all three journals over the years. In particular, we would like to thank all of our Associate Editors, Editorial and Advisory Board members, authors and referees, without whom none of this would have been possible.

With another successful year in the bag, we hope you will join us in making this year even better…

Read more about the 2011 Impact Factors from across RSC Publishing on the RSC Publishing Blog.