Brushing the Pain Away

In spite of the unparalleled advances in drug discovery, developing a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge. The beguiling...
Read More

Broken Rice Grains to Iron-Rich Meal

Fortifying rice is a way to help improve nutrition and one scientist steps up to the plate to use low-value broken grains to become iron-rich meals for Filipinos. Dr. Imelda Angeles-Agdeppa has a...
Read More

Proper Handwashing

Practice proper handwashing especially before preparing food for your family, friends or customers. Here’s a simple guide from DOST which is also based on various Food Safety Materials of FDA,...
Read More

Knocking Out Superbugs

For about a century, antibacterial drugs known as antibiotic have helped control and annihilate many for the life-threatening microorganisms that make us sick. However, in recent years, antibiotics...
Read More

Plant-derived Insulin Mimetics: The Long-awaited Cure for Diabetes

Diabetes mellitus, a chronic and the most common metabolic disease, affects 285 million people worldwide. The number of people getting affected is increasing every year, faster than the rate...
Read More

IN THE SPOTLIGHT

Brushing the Pain Away

pills-140186_1280

In spite of the unparalleled advances in drug discovery, developing a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.

The beguiling ability to treat fever and pain can be traced back to 3.5 thousand years ago, when the Greek physician Hippocrates prescribed an extract from willow bark and leaves. Later in the 17th century, the biologically active substance of the willow bark, salicin (or salicylic acid), was identified in Europe through chemical degradation. The Kolbe company, operating at that time in Germany (in 1860), started scaling up the production of salicylic acid.

However, salicylic acid was associated with gastrointestinal (GI) irritation due to its acidic nature. Hence, the more palatable acetylsalicylic acid, now known commercially as aspirin, was launched in the market by Bayer in 1899.

Today, medication of inflammatory-related diseases is largely based on interjecting the action of mediators that propel the host’s response to injury. Non-steroidal anti-inflammatories, steroids and antihistamines, for instance, were developed on this concept.

The success of non-steroidal anti-inflammatory drugs (NSAIDs) in remedying various inflammatory conditions such as rheumatoid arthritis and osteoarthritis supported the hypothesis that blocking the enzyme prostaglandin H synthase or cyclooxygenase (COX) may be the key to the discovery of anti-inflammatory drugs.

Sadly, widespread NSAID use is associated with GI irritations and toxicities, making it a chief problem during long-term therapy.

The good news is that several medical reports have shown that traditional NSAIDs may fight off cancer. For example, the commercial anti-pain drugs sulindac and indomethacin show therapeutic effects against colorectal cancer.

Then it was discovered that an enzyme isoform – COX-2 – is present at high levels in a wide variety of cancer tissues, such as colon, breast, prostate, and pancreas. Moreover, it seems to control many cellular and other biological processes.

Thus, selective COX-2 drugs have been comprehensively explored in the treatment and preclusion of a variety of cancers. COX-2 inhibitors block COX-2 enzyme and not the COX-1 enzyme, thus impending the production of COX-2 which is more often the cause of pain and swelling of inflammation and other painful conditions. These drugs are different from traditional NSAIDs which usually block both COX-1 and COX-2 enzymes.

Though the selective COX-2 inhibitor commercial drug celecoxib induces programmed cell death in human prostate cancer cell lines, while the use of rofecoxib in preventing the recurrence of colon polyps was associated with adverse cardiovascular incidences. This puts a shadow of doubt on the long-term use of selective COX-2 inhibitors on cancer chemoprevention, and highlights the need to develop anti-inflammatory and analgesic agents that do not put patients at risk for gastrointestinal irritation or heart attack.

In our search for such drugs, we became interested in finding excellent acceptor-driven biological activity. The prevalence of unsaturated five-membered oxocarbocyclic motifs in anti-inflammtory and anti-cancer natural products and other bioactive compounds provides stimuli to discover potential anti-inflammatory and anti-cancer agents through a diversity-oriented synthesis approach.

Cyclopentanone platforms are present among natural and non-natural anti-inflammatory and anti-cancer compounds. Such substances play important roles in chemistry and biology because they are susceptible to addition reactions with biological groups present in proteins and enzymes associated with cancer-cells and inflammatory factors. Many biologically active cyclopentenone derivatives have been identified from nature (e.g. marine and terrestrial-derived fungi, liverwort, and plants) and block diverse biological activities, including anti-cancer, anti-inflammatory, cycloxyenase 2 (COX-2) inhibitory, cytotoxic, antimicrobial, anti-pigment, and plant growth-regulatory activities.

Currently in drug discovery, irreversible binding in active sites has proven to be one answer to drug resistance in cancer treatment. Overall, compounds containing the unsaturated carbonyl unit possess multiple biological activities that could be transferred into novel pharmaceutical agents. It has been shown that cancer and inflammatory conditions are connected, which makes these compound types even more attractive as therapeutic agents. The ability of unsaturated carbonyl to modify active site cysteines, resulting in irreversible inhibition of an enzyme is an emerging area in drug discovery.

The diversity-oriented synthesis (DOS) approach to construct a variety of 4-heterocyclopentenone derivatives allows the preparation of new compounds with increased and promising anti-inflammatory activity. Extensive literature search provides little evidence on DOS studies related to anti-inflammatory and cytostatic unsaturated cyclopentanones.

Our study hopes to synthetically prepare a variety of simple, low-molecular weight, functionalized, cyclopentanone derivatives with promising anti-inflammatory activity targeting enzymes involved in the inflammatory biochemical cascades such as COX and anti-cancer activity against a selected panel of cell-lines. The products that will be identified may feature new and unusual biological mechanism which would be high interest to medicinal chemists. In addition, the new structures generated would be viable templates for generating further a library of synthetic derivatives with improved potency.

NSAIDs embody an important type of compound to treat pain and cancer. The fast discovery of selective COX-2 inhibitors and anti-cancer compounds can be ascribed to rational drug design strategies. Sadly, the cardiovascular (CNS) side effects related with selective COX-2 inhibitors underscore the drawbacks that may be confronted in this drug discovery project.

Indeed, in spite of the unparalleled advances in drug discovery, developing a safe, effective, and economical therapy for treating inflammatory conditions still presents a major challenge.

 

Written by: 
Allan Patrick g. Macabeo
University of Santo Tomas

Published by:Department of Science and Technology - Science and Technology Information Institute (DOST-STII)

Peptides and Small Molecules as Antidiabetic Drugs

In this research, peptide-based substances that block the breakdown of large sugar matter in the body and lower blood sugar levels will be produced and developed as antidiabetic drugs. The search for more potent antidiabetic drugs continues as diabetes mellitus, or...

read more

Proper Handwashing

Practice proper handwashing especially before preparing food for your family, friends or customers. Here’s a simple guide from DOST which is also based on various Food Safety Materials of FDA, ServSafe, and USDA.   DOST offers training and technical assistance...

read more

Knocking Out Superbugs

For about a century, antibacterial drugs known as antibiotic have helped control and annihilate many for the life-threatening microorganisms that make us sick. However, in recent years, antibiotics have been losing their punch against several types of bacteria. A...

read more

Archives

Categories

We Are OneExpert

Hello. We are One Expert. And we are ready to serve you in many ways.

Whether you’re a startup person who needs training for your new business or someone looking to hone activities that promote technology transfer and commercialization, productivity enhancement and technical capability, skills upgrading, we have programs well suited to your needs and objectives.

Android Mobile App

The Department of Science and Technology (DOST) One Expert has stepped up its campaign with the creation of a mobile app to improve access to consultants and clients that need S&T assistance. The mobile application will drive an easier and better engagement of people to meet the delivery of DOST programs.

MORE NEWS

Broken Rice Grains to Iron-Rich Meal

Fortifying rice is a way to help improve nutrition and one scientist steps up to the plate to use low-value broken grains to become iron-rich meals for Filipinos. Dr. Imelda Angeles-Agdeppa has a dream to make healthy, nutritious food more accessible to the public....

read more

Proper Handwashing

Practice proper handwashing especially before preparing food for your family, friends or customers. Here’s a simple guide from DOST which is also based on various Food Safety Materials of FDA, ServSafe, and USDA.   DOST offers training and technical assistance...

read more

Knocking Out Superbugs

For about a century, antibacterial drugs known as antibiotic have helped control and annihilate many for the life-threatening microorganisms that make us sick. However, in recent years, antibiotics have been losing their punch against several types of bacteria. A...

read more

Peptides and Small Molecules as Antidiabetic Drugs

In this research, peptide-based substances that block the breakdown of large sugar matter in the body and lower blood sugar levels will be produced and developed as antidiabetic drugs. The search for more potent antidiabetic drugs continues as diabetes mellitus, or...

read more

This coffee table book named Bridge, designed to link scientific minds to practical people that use the results of R&D. Bridge captures the goals of DOST in making science weave into the lives of people as expressed in DOST’s taglines “Agham na Ramdam” and “Science for the People.”

Brushing the Pain Away

In spite of the unparalleled advances in drug discovery, developing a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge. The beguiling ability to treat fever and pain can be traced back to 3.5 thousand years...

read more

Broken Rice Grains to Iron-Rich Meal

Fortifying rice is a way to help improve nutrition and one scientist steps up to the plate to use low-value broken grains to become iron-rich meals for Filipinos. Dr. Imelda Angeles-Agdeppa has a dream to make healthy, nutritious food more accessible to the public....

read more

Knocking Out Superbugs

For about a century, antibacterial drugs known as antibiotic have helped control and annihilate many for the life-threatening microorganisms that make us sick. However, in recent years, antibiotics have been losing their punch against several types of bacteria. A...

read more

Peptides and Small Molecules as Antidiabetic Drugs

In this research, peptide-based substances that block the breakdown of large sugar matter in the body and lower blood sugar levels will be produced and developed as antidiabetic drugs. The search for more potent antidiabetic drugs continues as diabetes mellitus, or...

read more

Chicken Egg for Therapy

I consider an encounter with a patient on the verge of dying due to a severe case of infection as one of my most humbling experiences as an internist. As part of routine care, I gave the patient the most effective drug under the circumstances, the most recommended...

read more

Finding the Gene

How many times do we hear people complain that drugs don’t work for them? Have you heard of people who have suffered from medicine-related side effects? How about people who hate taking medication because they fear possible side effects? In this advanced age of...

read more