Cardio Innovation: Ruthenium as Vasodilator

Cardiovascular diseases are the leading cause of death worldwide, according to the World Health Organization (WHO), representing approximately 31% of all global deaths. Cardiovascular diseases encompass conditions such as coronary artery disease, stroke (CVA), rheumatic heart disease, and other heart and blood vessel-related conditions. In Brazil, cardiovascular diseases are also one of the main causes of mortality, according to the Brazilian Ministry of Health. In 2019, cardiovascular diseases accounted for approximately 27% of all deaths in the country. Arterial hypertension is one of the main risk factors for cardiovascular diseases in Brazil and has been identified as associated with an increased risk of severe complications if individuals contract COVID-19. This is because the SARS-CoV-2 virus can cause inflammation and additional stress to the cardiovascular system. Impact on morbidity and mortality rates have shown that patients with COVID-19 and pre-existing cardiovascular diseases are more likely to require hospitalization, mechanical ventilation, and have a higher risk of death compared to patients without these conditions. Other contributing factors to cardiovascular diseases include Sedentary Lifestyle, where lack of regular physical activity is associated with a higher risk of cardiovascular diseases. Globally, it is estimated that 23% of adults and 81% of adolescents do not achieve recommended levels of physical activity; Unhealthy Diet and obesity, which are associated with a higher risk of developing cardiovascular diseases, including coronary artery disease, hypertension, and type 2 diabetes. Globally, more than 1.9 billion adults are overweight, and of these, more than 650 million are obese;  Smoking is a significant risk factor for cardiovascular diseases. It is estimated that smoking is responsible for about 10% of deaths from cardiovascular diseases worldwide.
The solution being developed in this project is to develop a new therapeutic approach for cardiovascular diseases, exploring the potential of ruthenium complexes and using advanced synthesis and evaluation techniques to ensure the effectiveness and safety of the treatment. It is estimated that 17.9 million people died from cardiovascular diseases in 2016, representing 31% of all deaths globally, according to PAHO-WHO, with endothelial dysfunction being a central factor due to its influence on vascular regulation. The endothelium is a layer of cells that lines the inside of blood vessels and is responsible for regulating vasodilation and vasoconstriction. When the endothelium does not function properly, there is a reduction in the production of nitric oxide, leading to an imbalance in vascular relaxation pathways.
Nitric oxide is essential for maintaining healthy vascular function as it is a chemical messenger that relaxes smooth muscle cells lining the blood vessels, causing vasodilation and promoting the reduction of blood pressure. Therefore, restoring or enhancing nitric oxide production in endothelial cells is a therapeutic strategy that we are developing for the treatment and prevention of cardiovascular diseases.
Our research has focused on ruthenium complexes that have shown great potential in influencing biological processes, especially in the context of the cardiovascular system, suggesting that this molecule has a positive impact on vasorelaxation, which is a vital process in blood pressure regulation and the prevention of cardiovascular diseases. 

             Our solution aims to develop an innovative therapeutic approach for cardiovascular diseases, harnessing the potential of ruthenium complexes. We utilize advanced synthesis and evaluation techniques to ensure the efficacy and safety of the drug we are developing. The ruthenium-based metal compound promotes vasodilation and improves nitric oxide production. Our focus on ruthenium complexes, known for their biological influence, aims to enhance pharmacological efficacy in the treatment of cardiovascular diseases.

         Computational biology techniques such as ADMET, molecular docking, and systems biology help understand molecular interactions, optimize complex design, and identify more effective structures to promote vasodilation. Computational biology used in the research has been an essential tool in understanding the underlying molecular interactions of cardiovascular diseases, providing valuable insights into how molecules interact and how biological pathways are interconnected. This has helped identify new therapeutic targets and understand how different molecules communicate within the cardiovascular system.

        In the field of drug design, the molecular docking approach developed in the research helped identify the therapeutic compound (ruthenium) to be used, allowing for the prediction of interactions between ligands and targets for rapid and preliminary screening of the kinetic properties of molecules before in vitro assays, saving valuable time and resources. With low toxicity and promising pharmacological properties, this developed complex has shown potential as a cardiovascular medication and may shed light on the advanced treatment of debilitating cardiovascular diseases. Research results suggest that the created molecule "FOR777G" may be a promising alternative in the treatment of cardiovascular disorders.

Our solution is for those who suffer from cardiovascular diseases, including patients with conditions such as coronary artery disease, hypertension, heart failure, and other heart and blood vessel-related illnesses. These patients represent a significant population worldwide facing daily health challenges due to their cardiovascular conditions.

The target population for our solution includes individuals currently facing gaps in available treatments for cardiovascular diseases. Often, these patients encounter limitations in accessing effective medications or experience significant side effects with existing treatments. Additionally, some populations may be underrepresented or underserved due to financial, geographical, or cultural barriers in accessing appropriate cardiovascular healthcare.

Our solution seeks to significantly improve the quality of life for these patients by offering innovative and effective treatment for cardiovascular diseases. By developing a therapeutic approach based on ruthenium complexes, we are exploring new frontiers in cardiovascular medicine with the goal of providing a safe, effective, and low-impact treatment option for those suffering from heart conditions.

Through promoting vasodilation and improving nitric oxide production, our treatment aims to reduce symptoms associated with cardiovascular diseases, such as chest pain, shortness of breath, and fatigue, thereby improving the quality of life for patients. Additionally, the low toxicity and promising pharmacological properties of the ruthenium complex may mean fewer undesirable side effects compared to existing treatment options, providing a more tolerable treatment experience for patients.

By conducting research with synthesis and evaluation, and ensuring all safety measures are in place, supported by an ethics committee that has approved the research beforehand, we are ensuring the effectiveness and safety of the treatment, instilling confidence in potential investors in our solution to improve their cardiovascular health.

Our team is composed of individuals with diverse backgrounds and experiences, with this research being conceptualized and developed by the team leader, who is a junior high school researcher, supported by professionals from the Drug Research and Development Center (NPDM), linked to the Faculty of Medicine of the Federal University of Ceará - Brazil (UFC-BR) through the Department of Physiology and Pharmacology. The NPDM is the first structure in Brazil to work in all stages of the drug development chain, from molecule synthesis, through animal testing, to the final stage of research involving humans. The NPDM is a multidisciplinary structure with the potential to promote and conduct scientific studies, technological development, and innovation to meet the preclinical and clinical research necessary for the development of new drugs in the industry and in accordance with the policies and guidelines defined by the National Health Surveillance Agency (ANVISA), Ministry of Health (MS), Ministry of Science, Technology, and Innovation (MCTI). The structure of the Center consists of 28 laboratories for toxicological and pharmacological research; 60 individual offices for researchers, administrative area, hospital structure with 64 beds, 14 outpatient clinics, and an animal facility.

Our solution has a well-positioned team for those suffering from cardiovascular diseases, composed of a variety of healthcare professionals, researchers ranging from junior to doctoral level. The team leader for this idea has a deep understanding of the needs and challenges faced by the target population, as she is involved with people suffering from cardiovascular diseases. The implementation of the solution would be further developed at the NPDM by supportive sectors and patient groups that would provide valuable feedback throughout the process. Co-creation with the community would ensure that the solution is accessible and effective for those who will benefit from it. Overall, the diverse backgrounds and experiences of our team, combined with the sophisticated computational approaches developed in the research, and our commitment to developing an efficient medication for cardiovascular diseases, position us well to provide an impactful solution that meets the needs of our target population, which can lead to more efficient and personalized treatment for patients, tailored to their individual needs. In general, our solution aims to fill a critical gap in the treatment of cardiovascular diseases, providing a holistic, innovative, and effective therapeutic option for a population that currently faces challenges in accessing effective and low-risk treatments. By improving the cardiovascular health of these patients, our solution has the potential to positively impact their lives, allowing them to live with more comfort, autonomy, and well-being.

This work is a pilot because it represents an initial and crucial phase of the project, where we have conducted a series of activities to validate the feasibility and efficacy of our approach in the development of medications for cardiovascular diseases. So far, we have focused on several important steps:

1. We synthesized the metalocompound cis-[RuNO2)(bpy)2(4-phpy)]+ and characterized its structure to ensure its quality and purity.

2. We performed simulations of the pharmacokinetics and in silico toxicity of this molecule, using advanced computational methods to predict its behavior in the human body.

3. We built an interactome of biological pathways related to vasorelaxation and vasodilation, identifying the possible pathways of action of the metalocompound and elucidating its potential mechanism of action.

4. We conducted molecular docking studies to understand the interactions between the metalocompound and key proteins involved in the regulation of vascular tone, providing valuable insights into how the molecule may affect these biological processes.

5. We obtained approval from the university's ethics committee to conduct tests on the aorta artery.

6. We performed stability, viability, and biological activity tests of aorta rings in the presence of the metalocompound, verifying its impact on vascular tissues under controlled conditions.

7. We evaluated the vasodilatory action of the metalocompound in aorta rings with and without endothelium, comparing it with vasodilation controls to determine its efficacy and selectivity.

8. We investigated the possible mechanism of action of the metalocompound, focusing on the nitric oxide pathway, through the use of pharmacological blockers to better understand its effects on the cardiovascular system.

9. We statistically analyzed the results obtained in the experiments, using appropriate tests to assess the significance of the observed differences and ensure the robustness of our data.

So far, these activities have allowed us to gain a deeper understanding of the therapeutic potential of the metalocompound for the treatment of cardiovascular diseases. Although we are still in the early stage of the project, the preliminary results are promising and provide us with a solid foundation to advance to the next phases.

Developing an innovative solution for cardiovascular diseases requires specialized technical knowledge and access to advanced technologies. We believe that Solve can help us access technical resources, such as equipped laboratories and experts in various fields, as well as assist in addressing legal issues, which are essential requirements for the development and commercialization of medications. Solve can connect us with consultants specialized in health and regulations, as well as help facilitate partnerships with institutions experienced in legal issues related to health.

The introduction of a new therapy in the healthcare market requires a solid understanding of market dynamics, competition, and consumer demand. Solve can provide us with market insights and connect us with strategic partners, such as pharmaceutical companies or healthcare service providers, to help market and distribute our solution effectively.

In summary, we hope that Solve will assist us by connecting us to knowledge, outreach, resources, potential funders, investors, or institutions that can provide support to advance, as well as partnerships that help us overcome various difficulties for the successful development and implementation of our solution.

Our solution is innovative because we are developing a therapeutic approach based on a little-explored metalocompound in the treatment of cardiovascular diseases. By using this new class of metallic compounds, we are introducing an innovative perspective in the field of cardiovascular medicine, potentially offering an effective and safe alternative for patients.

Additionally, our solution aims to improve the production of nitric oxide, a crucial component in the regulation of vascular tone and blood pressure. By promoting vasodilation and relaxation of blood vessels, our treatment can help reduce the symptoms associated with cardiovascular diseases.

By introducing this new therapeutic approach, we hope to catalyze broader positive impacts in this space. For example, our research may stimulate interest in ruthenium compounds and their application in other areas of medicine beyond cardiovascular diseases, such as for people with glaucoma, as observed by the team. Additionally, by providing a differentiated therapeutic option, we can positively influence the market for cardiovascular drugs and even change the landscape of cardiovascular health.

In summary, our solution is innovative because it introduces a new class of therapeutic compounds and addresses the problem of cardiovascular diseases in a significantly improved way, potentially offering substantial benefits to patients and broader impacts in the field of cardiovascular medicine.

As we are developing a therapeutic approach based on an underexplored metal compound, we hope to offer a safe and effective alternative for patients facing limitations in accessing existing medications or experiencing significant side effects with conventional treatments. Our research also holds the potential to expand to other medical conditions and to stimulate interest in ruthenium compounds and their application in areas beyond cardiovascular diseases. The innovation we are introducing may have a broader impact on the field of medicine, and we expect our solution to improve the quality of life for patients with cardiovascular diseases.

Our main impact goal is to reduce morbidity and mortality related to cardiovascular diseases by providing effective and affordable treatment. To measure our progress, we intend to track indicators such as the incidence and mortality rate of cardiovascular diseases in the target population before and after the implementation of our solution. Additionally, we are monitoring treatment accessibility by measuring the number of patients who are able to receive adequate care, especially in remote or low-income areas. Other indicators include clinical outcomes such as blood pressure reduction and prevention of adverse cardiovascular events.

The main technology driving our solution is computational biology. We use advanced molecular modeling techniques such as ADMET, molecular docking, and systems biology to understand the underlying molecular processes of ruthenium compounds' interactions with biological pathways. This allows us to optimize the effectiveness of ruthenium complexes in promoting vasorelaxation and preventing cardiovascular diseases. Additionally, our approach combines modern techniques in organic compound synthesis with traditional knowledge in medicinal chemistry to develop innovative and affordable treatments for patients with cardiovascular diseases.

6 people

"1 year"

We are committed to promoting diversity, equity, and inclusion in our team, recognizing that this not only strengthens our work environment but also empowers us to achieve more meaningful and impactful results in our problem-solving efforts.

Our business model involves developing a product initially through research, testing, and clinical trials, and refining a metalocompound that will aid in the treatment of cardiovascular diseases. This compound will be available in the form of medication, with a medical prescription. Our main focus is to provide value both to patients suffering from cardiovascular diseases and to the medical and scientific community.

We will seek to establish partnerships with pharmaceutical companies or other organizations in the healthcare sector to assist in the widespread distribution and commercialization of our product. These partnerships may include licensing agreements, co-development, or co-marketing agreements, allowing us to expand our reach and increase sales.  We are open to raising capital from investors interested in supporting the development and commercialization of our metalocompound. This can be done through funding rounds, where investors acquire ownership stakes in the company in exchange for funding.