Project Title: Reactivity-guided design and chemical synthesis of Berberine analogs towards photodynamic treatment of cancer and high throughput virtual screening of targeted compounds towards strategic therapeutic approaches in treating SARS-CoV2
BASIS Advisor: Dr. Ivana Bozidarevic
Internship Location: Aspiring Scholars Directed Research Program
Onsite Mentor: Edward Njoo
In drug development and medicine, there are many different methods and strategies that can be pursued in designing novel small molecule therapeutics. One way to design pharmaceuticals is through thinking about reactivity, whether that is the reaction of a molecule with the target or possible reactions that can be done to modify the molecule. Berberine, a natural product extracted from plants in the genus Berberis, has been demonstrated to have various biological activities including and the ability to bind to DNA, antibacterial effects, cytotoxic effects, and antitumor properties. The known biological activity of berberine, along with its long history in traditional medicine and its current use as a dietary supplement marketed to individuals with type II diabetes, high blood pressure, and high cholesterol, has made it a compound of interest to medicinal and organic chemists. Synthetic modifications can be done to different carbon positions of berberine, and the products of those reactions can be screened to see if they result in more potent biological activity. Science and research responds to the current issues in society, and as the novel coronavirus pandemic, which first emerged in Wuhan, China in December of 2019, quickly spread across the globe and changed the structure of our society and daily lives, research towards the development of possible inhibitors and vaccines became of huge interest. Potential inhibitors of SARS-CoV-2 main protease, which play a role in viral replication, and the spike glycoprotein, which is essential for cellular entry, were designed based on known reactivity between the target and the compounds. Computational screening of the inhibitors developed through de novo molecular design allow us to identify compounds that may be effective against the coronavirus in humans. Methodology in the research of these two projects demonstrate how reactivity can serve as the basis of drug design.
My final presentation! Thanks to Dr. Bozidarevic, Edward Njoo, my coworkers, and the organizations that provided funding and instrumentation support.
While this post may mark the end of my senior project, it definitely doesn’t mean that research on berberine and related analogs ends. Throughout the past couple of weeks, I have synthesized novel berberine analogs, conducted in-vitro, in-vivo, and ex-vivo experiments, and completed computational screening of a library of berberine analogs. Alongside my work with […]
One of the many reported activities of berberine that I am interested in is the antibacterial activity of berberine. It has been previously reported that berberine and related analogs have cytotoxic effects against methicillin-resistant Staphylococcus aureus (MRSA) when working in synergy with other antibiotics such as ampicillin. This led us to wonder about berberine’s antibacterial […]
Last week, I introduced one way that the novel coronavirus, SARS-CoV2 can be targeted by small molecule therapeutics, which is designing a peptidomic molecule to target the main protease of the coronavirus. There are many other aspects of the novel coronavirus that can be targeted by the design of novel inhibitors, an example of such […]
As the novel coronavirus pandemic rapidly spreads and more and more research is conducted everyday, new information is revealed. Research on this novel coronavirus started almost immediately, with many researchers either adding it on top of their current research or even completely shifting gears. Even as a high schooler, I could do the same thing, […]
Since the lab has been closed since shelter in place started, the past few weeks have been filled with a lot of in-silico screening, such as running DFTs and completing docking analysis (explained in last week’s blog post!) of the compounds that we have previously synthesized and also compounds that we hope to be able […]
Over the past couple of weeks, our lives as we know it has been turned upside down. The novel coronavirus pandemic has spread around the world and affected over 1 million individuals, pushing healthcare systems to their limits and causing panic. However, this pandemic does highlight one positive aspect regarding science. The volume of research […]
Having a pure compound is not all the end of the process for a chemist; it’s just the first step. Next is determining what that compound is. Even though we try our best to predict what the products may be, we aren’t always right. There are many different characterization methods depending on what a chemist […]
Now that you have some background about what berberine is and some reactions that I want to complete in the coming weeks, I’m sure some of you are wondering what on earth synthetic organic chemists spend their long hours in the lab doing. When I first started working in the lab in summer, I thought […]
Last week, I introduced what berberine is, and some of the background behind it, in particular, why berberine is of interest in the field of medicine. In the coming weeks, I plan to synthesize novel berberine derivatives and screen them in-vivo and in-vitro for biological activity. Along this, I will be completing in-silico screening of the derivatives, which entails computational […]
Within the last century, leaps and bounds have been made in medicine, including the development of novel therapeutic agents and vaccinations that have resulted in the eradication of diseases in many first world countries. In fact, a quick comparison between the volume of research conducted after the SARS outbreak in 2001 and the research that […]