Synthesis of natural product analogs as small molecule inhibitors

ABSTRACT Natural products with interesting unique structures and special biological activities possess great potential in the development of novel pharmaceuticals. However, the evaluation of biological activity is always limited due to the low yield and difficulty of separation from plants and microorganisms. Synthetic organic chemistry provides an alternative tool to create such natural products from accessible materials. A huge mission for organic chemists is to develop novel strategies to produce natural products and their analogs in lab, as well as in quantitative scales. With this in mind, we have designed small molecule inhibitors towards Porcine reproductive and respiratory syndrome virus (PRRSV) and developed the synthetic routes to natural products psoracorylifols and furomollugin. In addition, a novel palladium nanoparticle catalyst was evaluated with the Suzuki-Miyaura reaction of aryl chloride. Chapter one describes the design and synthesis of small molecule inhibitors of PRRSV. Natural 1-(E)- Atractylodinol was successfully produced in a seven-step direct route. More analogs with antiviral activity were synthesized based on this natural product. The goal to design a cost effective antiviral drug towards PRRSV was achieved. The design of an approach to the unique 6,8-dioxabicyclo[3.2.1]octane skeleton in psoracorylifols B and C is discussed in chapter two. This special core structure was constructed via ketal formation in five steps. The novel direct synthetic route to furomollugin is introduced in chapter 3. Furomollugin was synthesized by utilizing the Hauser-Kraus annulation as a key step. The last chapter focuses on the evaluation and application of a novel palladium catalyst developed by Datye and co-workers. The utility of Datye catalyst was demonstrated in the Suzuki-Miyaura reaction of aryl chlorides and boronic acids. This catalyst showed great catalytic activity when aryl chlorides and aryl bromides were used for the Suzuki coupling in water media

A review on photothermal conversion of solar energy with nanomaterials and nanostructures: from fundamentals to applications

Solar energy is a green, sustainable, and de facto inexhaustible energy source for mankind. The conversion of solar energy into other forms of energy has attracted extensive research interest due to climate change and the energy crisis. Among all the solar energy conversion technologies, photothermal conversion of solar energy exhibits unique advantages when applied for water purification, desalination, high-temperature heterogeneous catalysis, anti-bacterial treatments, and deicing. In this review, the various photothermal conversion mechanisms based on different forms of heat release are summarized and some of the latest examples are presented. In addition, the necessary prerequisites for solar-driven photothermal materials toward their practical applications are also discussed. Further, the latest advances in photothermal conversion of solar energy are discussed, focusing on different types of photothermal applications. Finally, a summary is given and the challenges and opportunities in the photothermal conversion of solar energy are presented. This review aims to give a comprehensive understanding of emerging solar energy conversion technologies based on the photothermal effect, especially by using nanomaterials and nanostructures

Research progress of MicroRNA in podocytes autophagy in diabetic nephropathy

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes, and is a kind of abnormal microangiopathy of kidney structure, function or clinical indicators caused by diabetes. Podocyte injury has been considered as a major contributor to the progression of diabetic nephropathy(DN). microRNA can participate in podocytes injury through autophagy.In this paper, the mechanism of microRNA involved in DN podocytes autophagy was reviewed to provide reference for the treatment of DN in the future

Three-dimensional shape analysis of peripapillary retinal pigment epithelium-basement membrane layer based on OCT radial images

The peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer angle was recently proposed as a potential index for estimating intracranial pressure noninvasively. However, the ppRPE/BM layer angle, measured from the optical coherence tomography (OCT) scans, varied across the radial directions of the optic disc. This made the ppRPE/BM layer angle difficult to be utilized in its full potential. In this study, we developed a mathematical model to quantify the ppRPE/BM layer angles across radial scans in relation to the ppRPE/BM 3D morphology in terms of its 3D angle and scanning tilt angles. Results showed that the variations of the ppRPE/BM layer angle across radial scans were well explained by its 3D angle and scanning tilt angles. The ppRPE/BM layer 3D angle was reversely fitted from the measured ppRPE/BM layer angles across radial directions with application to six eyes from four patients, who underwent medically necessary lumbar puncture. The fitted curve from our mathematical model matched well with the experimental measurements (R2 \u3e 0.9 in most cases). This further validated our mathematical model. The proposed model in this study has elucidated the variations of ppRPE/BM layer angle across 2D radial scans from the perspective of the ppRPE/BM layer 3D morphology. It is expected that the ppRPE/BM layer 3D angle developed in this study could be further exploited as a new biomarker for the optic disc

Computer-Assisted Analysis of Soccer Ball Trauma of the Eye

Purpose: Sports-related eye injuries are common in the United States and around the world, particularly in youth. Over half of patients presenting with these injuries are of 18 years or younger, and sports and recreation account for nearly a quarter of all pediatric eye injuries treated in US emergency departments. Soccer is the most popular game in the world and is the leading source of sports-related eye injury in Europe and Israel. Soccer injuries cause visual impairment at a disproportionately higher rate than other sports. This study investigates the mechanisms of injury. Methods: A finite element simulation was developed to study the distribution of stresses in the eye following the impact of a soccer ball. The eye model was composed of sclera, vitreous, and retina. The retina was simulated as three layers: preretinal, intraretinal, and subretinal. Vitreoretinal adhesions were incorporated along retinal vessels. Results: The anterior pole experienced a peak stress of 69.8 kPa following impact of the soccer ball. The impact induced a pressure wave within the vitreous that traveled latitudinally along the anterior-posterior axis and repeatedly reflected from the intraocular tissue. Oscillations of high and negative pressure in the vitreous resulting from the pressure wave were greatest at the posterior pole. Stresses within the retina were highest along the retinal vasculature, especially at the distal bifurcations where the peak stress was 15.4 kPa. The subretinal layer experienced more stress than the preretinal and intraretinal layers except along the vasculature, at which the preretinal layer experienced more stress. Conclusions: The distribution of stresses within the eye quantify and expand on frequently proposed biomechanical bases for ocular injuries resulting from soccer ball trauma. High stress near the point of impact may account for commonly observed anterior segment injuries. Negative pressures within the vitreous adjacent to the posterior retina provide further support for the anterior pulling of the retina as a potential mechanism for posteriorly localized retinal lesions. These patterns of stress throughout the eye highlight the importance of eye protection in soccer and other sports, which have been demonstrated to prevent up to 90% of ocular injury.https://digitalcommons.unmc.edu/chri_forum/1035/thumbnail.jp