Spring’s ‘Design A Molecule Competition’ was Cresset’s fourth and the third to have an anti-malarial flavor. Contestants were asked to design a molecule with a target relevant to antibacterials and anti-fungals.
Cresset was delighted with the response to the competition. The resultant entry molecules were ranked relative to the original bioactive/bound conformer using Cresset’s ‘3D Molecular Field Similarity’ in FieldAlign and then judged on synthetic tractability and drug-likeness. Novelty was also factored into the ranking by imposing a 2D similarity penalty.
Winner: Congratulations to Albert Kooistra (PhD student in the division of Medicinal Chemistry of VU University Amsterdam), the winner of an iPad!
Albert ‘s winning entry won on the grounds of its combination of simplicity, 2D dissimilarity from the template, fit to the protein pocket and (more subjectively) on its tractability and logP / TPSA profile. The design is simple and compact with a nice fit to the pocket. The zwitterionic piperidine fragment provides the necessary twist in the molecule – that is normally induced by ortho-chloro substituents in the parent Triclosan – and potential backbone H-bonding interactions. The addition of this polar fragment also serves to counter the overall high lipophilicity exacerbated by the alkyl thiophene substituent (although maybe too far?).
Image: Winning entry Albert Kooistra, 2D and 3D (modelled in ENR)
In response to hearing about his success winning the competition Albert said: “I really enjoyed competing and using your FieldAlign tool again. Compared to the previous competition (in which I was kindly awarded a 2nd prize) this was a whole new challenge due to the different reference molecule and of course the different target.”
There were many other good entries which were running very close on Albert’s heels, namely: Anthony Nahoum (Strathclyde University) who submitted a couple of nice examples; many imaginative and diverse entries from both Chris Swain (Consultant) and Andrew Lima (4th year student Cardiff University). Well done to all!
Cresset has no commercial interest in exploiting IP from its competitions and so with consent from contestants we are very happy to disclose the winning structures.
Cresset’s Design a Molecule Competition is not only a great way to hone your molecule design skills, but to generate potential leads in the fight against malaria, which is why any IP generated from the competition will be donated to a not-for profit working on this very worthy cause. In preparation for next time you can familiarize yourself with the last competition, or download a demo of our products.