RSC Medicinal Chemistry Blog

Take a look at the top 5 most downloaded MedChemComm articles in 2012 and blog your thoughts and comments below.

The developability of heteroaromatic and heteroaliphatic rings – do some have a better pedigree as potential drug molecules than others?
Timothy J. Ritchie, Simon J. F. Macdonald, Simon Peace, Stephen D. Pickett and Christopher N. Luscombe
Med. Chem. Commun., 2012,3, 1062-1069, DOI: 10.1039/C2MD20111A

Gd(III) chelates for MRI contrast agents: from high relaxivity to “smart”, from blood pool to blood–brain barrier permeable
Chang-Tong Yang and Kai-Hsiang Chuang
Med. Chem. Commun., 2012,3, 552-565, DOI: 10.1039/C2MD00279E

The use of phosphate bioisosteres in medicinal chemistry and chemical biology
Thomas S. Elliott, Aine Slowey, Yulin Ye and Stuart J. Conway
Med. Chem. Commun., 2012,3, 735-751, DOI: 10.1039/C2MD20079A

Inhibition of bromodomain-mediated protein–protein interactions as a novel therapeutic strategy
Silviya D. Furdas, Luca Carlino, Wolfgang Sippl and Manfred Jung
Med. Chem. Commun., 2012,3, 123-134, DOI: 10.1039/C1MD00201E

Development of second generation epigenetic agents
Philip Jones
Med. Chem. Commun., 2012,3, 135-161, DOI: 10.1039/C1MD00199J

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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.

MedChemComm Editor Richard Kelly will be visiting several North East universities next week as part of the RSC US Roadshows 2012.

Week 4 sees the Royal Society of Chemistry visiting four universities in Pennsylvania and New York:

May 7th – University of Pittsburgh

May 8th – Pennsylvania State University

May 10th – University of Pennsylvania

May 11th – Columbia University

Read more about the US roadshows 2012:

Starting in mid April 2012, RSC Publishing has been touring the United States of America to share more than 170 years experience of publishing in the chemical sciences. Sixteen universities across the country are hosting these one-day events, which are open to all members of the hosting institute.

Attendees have the opportunity to explore RSC’s apps on mobile devices and meet informally with RSC editors. Lunchtime discussion groups explore reading habits and opportunities in the 21st century and an afternoon seminar give an insight into the world of scholarly publishing, with tips on how to get published in high impact journals. A demonstration of ChemSpider, and a guest lecture from an RSC associate editor or board member are available at many of the roadshows.

Follow the RSC Roadshows on Twitter – just look for #RSC2012.

Goverdhan Mehta talks to Sheena Elliott and Elinor Richards about the progress of science in India and the challenges scientists face

Goverdhan Mehta is a researcher, specialising in organic synthesis. He has helped to build institutions in India – the Indian Institute of Technology, Kanpur, the University of Hyderabad, and the Indian Institute of Science, Bangalore. He was director of the Indian Institute of Science (1998-2005) and vice chancellor of the University of Hyderabad (1994-1998).

Your research is focused on organic chemistry. What attracted you to that field?

There is something intrinsically fascinating about organic chemistry. In my early high school years, when I was exposed to interesting chemical structures, I was attracted to them. I had a sense of appreciation for art and organic molecules to me provided a wonderful expression of art at a molecular level.

What are your main achievements in the field?

I have worked in many areas of organic chemistry, but it’s synthesis that’s given me the greatest pleasure. As organic chemistry advanced, different contemporary challenges came to my attention. The main driver for me to pursue those challenges was the intricacy of the target structure synthesis. There was also an element of expectation that perhaps our research might become useful to society. We continue to need new drugs for a variety of disorders, so we synthesised a large number of natural products; many of them are biologically active and it is quite possible that some of them can provide leads for new drug discovery.

Over the last few years, I have become interested in how to address a problem that the ageing population is facing – neurodegeneration. It has been shown that some natural products can slow down neurodegeneration. In some cases, there is also an indication that they can help restore lost cognitive function. So I have been working on the synthesis of such lead molecules. As I’m getting older, I recognise the need for doing something in that area!

You’ve won numerous awards. Which achievements are you most proud of?

I don’t think that awards and recognition have necessarily brought me a great sense of joy. They do bring a sense of satisfaction because your peers have recognised your work. But I don’t think any serious researcher works for awards. It is the sheer joy of research that keeps people going. Recognition has come my way, but don’t think that I can equate that with the joy of doing research.

What are the challenges facing scientists in India and how could these be overcome?

Scientists all over the world are facing challenges on two fronts. The first problem is that scientists are not being supported by society as much as they should and some governments are not always forthcoming in terms of providing budgetary support. The second problem is that scientists, and science in general, have become isolated both in terms of discipline and, to some extent, in terms of geographical location. This is being redressed now with increasing international collaborations, so in the geographical sense, the isolation is being reduced. But I think disciplinary isolation vis a vis other knowledge streams and fragmentation of science is still a serious challenge.

It is a good time for scientists in India because the government is very supportive of science. Funding is no longer as serious a problem as it is in other parts of the world. Recently, our prime minister said that the budget for science will be almost doubled over the next few years. But I’m not too sure that we as a scientific community are steering science in India in the direction that it ought to be heading. I believe that the government and the scientific community must set a goal that in the next 10 years, India will be among the world’s leading scientific countries.

What is your opinion on the perception that Indian science and research is falling behind the rest of the world, following recent comments by Prime Minister Manmohan Singh?

Prime Minister Singh’s statement referred mainly to China. China has made more progress in science and technology than India. Scientific productivity in India has increased, but not as much as in China. Since we are behind, to simply say that we are walking and walking well is not enough. We should be galloping to catch up. My judgement is that our progress is not commensurate with the support that the government is providing, and not commensurate with the capacity, capability, enthusiasm and the vibrancy that our youth have. We can achieve much more.

How do the different industries compare (the pharmaceutical industry in particular or the more general chemical industry)?

It is only over the last 10 or 12 years, since the economic reforms, that industry in India has grown at such a rate so as to be in a position to invest in research and development. I expect that investment by industry is going to rise; however, the current level of investment is not in an acceptable range. There are certain sectors – pharma, for example – and some other chemical industries, where I think India’s potential is immense, but there are some challenges with the policies that are being pursued. We have to devise a well thought out strategy.

The prime minister’s Science Advisory Council reported that there in an absence of any Indian universities among the world’s best. What is your opinion on the quality of universities in India?

I’m not a great believer in the ranking systems being followed, but the fact is that no Indian university features among the top few hundred  universities. However, if we were to look at undergraduate teaching, India has institutions that produce graduates through excellent teaching and training. The graduates are probably as good as they are anywhere else in the world. If you were to grade an institution on the quality of undergraduates, I would say that the Indian Institutes of Technology rank among the top 10 institutions in the world. But, if you bring in research and other elements, they will not feature anywhere near the top. So the quality of research is a serious problem. I think it is high time that the scientific community and scientific leadership in our country sort out an effective, implementable strategy to make a major shift.

You experienced difficulty obtaining a visa to travel to the US in 2006, when you were invited to give a lecture at the University of Florida. At the time, a report from the National Academy of Sciences in the US said that at least 3000 scientists had faced a similar problem. Have things improved since then or do you believe that the visa problem is hampering scientific progress and career development for scientists?

It was ironic that I and a leading scientist from the US, Jane Lubchenco (who at that time was president of the International Council for Science before I succeeded her), wrote an editorial about the principle of universatility of science and the visa regime in Science a few months before this happened. We wrote that it was important for the international growth of science that scientists were able to travel. Little did I realise that soon I would be a victim of this! I think the situation has improved, but a lot more needs to be done. While the US National Academy of Sciences is playing a very positive role towards this end, the academies can only do the advocacy. Eventually, it is the government and the state department of security staff that makes the final judgement.

If you have any spare time, how do you fill it?

For most scientists, and I’m no exception, your research is a hobby. What other profession can give you that pleasure and privilege? In a previous interview, I was asked what I would wish for. I said we Indians believe in rebirth and so the only wish I have is that if I were to be born again, I would be a scientist. I would like to be a chemist, hopefully a better one.

Read some of Goverdhan Mehta’s recent research:

Towards a temperature-guided molecular switch: an unusual reversible low-temperature polymorphic phase transition in a conformationally locked environment
Goverdhan Mehta and Saikat Sen, Chem. Commun., 2009, 5981
DOI: 10.1039/b905651c

Understanding the self-assembling process in crystalline cyclooctitols: an insight into the conformational flexibility of medium-sized rings
Goverdhan Mehta, Saikat Sen and Kotapalli Pallavi, CrystEngComm, 2008, 10, 534
DOI: 10.1039/b712877k

Additive induced polymorphous behavior of a conformationally locked hexol
Goverdhan Mehta, Saikat Sen and Kailasam Venkatesan, CrystEngComm, 2007, 9, 144
DOI: 10.1039/b613949c