Title

Modifying the Molecular Structure of Ritalin to Extend Its Duration of Action

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Abstract

Ritalin is an effective medicine used to treat Attention Deficit Hyperactivity Disorder (ADHD). Ritalin, also known as methylphenidate, held the stage for the most used and widespread medication for ADHD, until others like Dexedrine, Adderall, and Focalin were developed. Ritalin’s flaw is a short duration of action- approximately 3.5 hours. This lends to frequent redosing, which is inconvenient and can lead to issues with missed doses. Ritalin’s duration of action is affected by its metabolism in its targeted enzyme, Human Hepatic Carboxylesterase 1 (hHCE-1). Our research goal was to modify the chemical structure of Ritalin to increase its duration of action. The short duration of action can be attributed to how quickly the Ester group of Ritalin gets cleaved by amino acids in hHCE-1’s active site. To approach this, we designed different modifications of Ritalin in Avogadro (a molecule editor program) to add a modification that would act as a shield to protect the Ester from getting cleaved, increasing the duration of action. The various modified Ritalin structures were docked in PyRx (a Virtual Screening Tool for drug design). There, we could observe the orientation of the modified drug in hHCE-1’s active site. In the end, we concluded that replacing the Ester’s R group with a tert-butyl functional group was most effective in altering the orientation of the Ritalin in hHCE-1’s active site to protect the Ester. However, this cannot be experimentally tested with our resources, so our results would have to be verified by organic chemists to ensure the molecule can be synthesized and is effective.

Location

HSS 202

Start Date

4-2-2022 11:15 AM

Presentation Format

Oral Only

Group Project

Yes

COinS
 
Apr 2nd, 11:15 AM

Modifying the Molecular Structure of Ritalin to Extend Its Duration of Action

HSS 202

Ritalin is an effective medicine used to treat Attention Deficit Hyperactivity Disorder (ADHD). Ritalin, also known as methylphenidate, held the stage for the most used and widespread medication for ADHD, until others like Dexedrine, Adderall, and Focalin were developed. Ritalin’s flaw is a short duration of action- approximately 3.5 hours. This lends to frequent redosing, which is inconvenient and can lead to issues with missed doses. Ritalin’s duration of action is affected by its metabolism in its targeted enzyme, Human Hepatic Carboxylesterase 1 (hHCE-1). Our research goal was to modify the chemical structure of Ritalin to increase its duration of action. The short duration of action can be attributed to how quickly the Ester group of Ritalin gets cleaved by amino acids in hHCE-1’s active site. To approach this, we designed different modifications of Ritalin in Avogadro (a molecule editor program) to add a modification that would act as a shield to protect the Ester from getting cleaved, increasing the duration of action. The various modified Ritalin structures were docked in PyRx (a Virtual Screening Tool for drug design). There, we could observe the orientation of the modified drug in hHCE-1’s active site. In the end, we concluded that replacing the Ester’s R group with a tert-butyl functional group was most effective in altering the orientation of the Ritalin in hHCE-1’s active site to protect the Ester. However, this cannot be experimentally tested with our resources, so our results would have to be verified by organic chemists to ensure the molecule can be synthesized and is effective.