New ARVs

The government has to stop deluding the public about an effective roll-out programme of antiretroviral drugs (ARVs) against HIV as there is simply not enough available nationally, says UCT's Professor Roger Hunter.

"I can't see how the amount of drug needed will materialise, so we really need to be taking the issue of producing the drugs here much more seriously," he said. Hunter holds the Mally Chair of Organic Chemistry at UCT.

Through HAART (highly active antiretroviral therapy), HIV is reportedly now only considered to be a chronic disease overseas, thanks to the limiting effects of antiretrovirals.

Hunter believes the HIV pandemic in the country should be fostering new development in the fine chemicals industry, taking the sector to "the next level, as is happening in India".

Apart from his research group's work on synthesising and developing novel bifunctional HIV reverse-transcriptase (RT) inhibitors, they are also involved in an ECOBIO Innovation-funded project with the Council for Scientific and Industrial Research (CSIR) to produce clinically-approved nucleoside RT inhibitors, AZT and d4T.

"The drugs we have targeted initially are still under patent to GlaxoSmithKline (AZT) and Bristol-Myers Squibb (d4T), but we are allowed to produce generic versions of them for Southern Africa provided we don't sell them overseas.

"It's unfortunately not recognised that new entities are likely to come from medicinal chemistry programmes and not directly from medicine, with organic synthesis the driving force."

Hunter's project with the CSIR in Johannesburg has resulted in the council forming a spinoff company, ARVIR.

"The joint project takes cheaply available guanosine, converting it biotechnologically, or enzymically, to 5-methyluridine and then using organic synthesis to get to the target drugs, which would be much cheaper and readily available."

Hunter said the combination of biotechnology with organic synthesis was a "potent marriage" promising great returns.

"The production of d4T is fairly straightforward; the challenge is to be able to reductively remove the hydroxyl group selectively at the 2'-position of the sugar in order to access the AZT skeleton. That way we could develop the process to access two types of drugs from a single precursor."

He said d4T was effectively in the bag and he was "reasonably confident" they would find a reagent and reaction conditions for the selective deoxygenation step to access AZT as there was significant literature precedent for this conversion.

"New process development would mean new intellectual property, something UCT is beginning to embrace as a highly desirable academic objective. It's a tricky balancing act, that of academic and business objectives. This project has a promising blend of the two."

Hunter said seeing a viable product within the context of medicinal chemistry had made a huge impact on the field of synthetic organic chemistry.

"We have the largest synthetic organic group in the country, with more than 30 MSc, PhD and postdoctoral students, involving Associate Professors David Gammon and Kelly Chibale and Dr Eugene Sickle.

"They all love making molecules."

The group also has new medicinal chemistry laboratories thanks to UCT.