Application of signal processing techniques for the spectroscopic analysis of dolutegravir and lamivudine: a comparative assessment and greenness appraisal.

HIV treatment has greatly improved over the years, with the introduction of antiretroviral drugs that target the virus and suppress its replication. Dolutegravir and lamivudine are two such antiretroviral drugs that are commonly used in HIV treatment regimens. Herein, three spectrophotometric methods manipulating ratio spectra were developed for the simultaneous analysis of dolutegravir and lamivudine in their binary mixtures. These methods include mathematical processing stages like ratio difference method or signal processing approaches such as the first derivative of the ratio spectra, and continuous wavelet transform. The developed spectrophotometric methods exploit the characteristic spectral differences between dolutegravir and lamivudine in order to quantify them simultaneously. These methods have shown promising results in terms of sensitivity and selectivity as validated per the ICH guidelines. Moreover, these methods offer a straightforward and economical alternative to more intricate analytical methodologies like high-performance liquid chromatography. By incorporating the analytical eco-scale and AGREE for greenness evaluation of the proposed methods, we can further ensure that these techniques are effective and environmentally friendly, aligning with the principles of green chemistry. This evaluation will provide a comprehensive understanding of the environmental friendliness of these spectrophotometric methods in pharmaceutical analysis.

Spectrofluorimetric determination of vitamin D in the serum of autistic and healthy children using functionalized graphene quantum dots.

Vitamin D is one of the most essential nutrients for brain development, and deficiencies during pregnancy and early childhood development might be associated with autism. Regular monitoring of serum 25-hydroxyvitamin D3 level could help in early diagnosis and therapy. Analytical measurement of serum 25-hydroxyvitamin D3 level using the traditional matrix-matched calibration technique yields inaccurate results due to absence of serum matrix free from 25-hydroxyvitamin D3. The aim of this work was to develop a validated spectrofluorimetric methodology based on the standard addition approach for quantifying 25-hydroxyvitamin D3 levels in real serum samples of autistic children. The spectrofluorimetric methodology utilizes functionalized graphene quantum dots as a fluorescent probe for selective quantification of 25-hydroxyvitamin D3 level, which is based on measuring the quenching properties of 25-hydroxyvitamin D3 on a fluorescent probe. The standard addition approach exhibits a minimal matrix interference since it identically utilizes the same matrix of each study sample for creating its own calibration curve. The method was validated using the guidelines outlined in ICH M10 draft for endogenous compounds quantification. The method was successfully applied for quantifying the serum 25-hydroxyvitamin D3 levels in autistic and healthy children, and autistic children had significantly lower serum 25-hydroxyvitamin D3 levels (with a mean ± SD of 23.80 ± 17.19) when compared to healthy children (with a mean ± SD of 50.13 ± 18.74, P < 0.001). These results suggested an association between vitamin D deficiency and autism.

Spectrofluorometric quantitative analysis of aripiprazole based on quenching of natural derived carbon quantum dots in spiked human plasma.

Autism spectrum disorder is a significant concern worldwide, particularly in Middle Eastern countries. Aripiprazole, a psychiatric medicine that works as a partial agonist at D2 receptors, is often used for autism-related behavior issues in children. Monitoring the therapy of aripiprazole could enhance the safety and effectiveness of treatment for autistic individuals. The purpose of this study was to develop a highly sensitive and environmentally friendly method for analysis of aripiprazole in plasma matrix. To achieve this, water-soluble N-carbon quantum dots were produced from a natural green precursor, guava fruit, and used in fluorescence quenching spectroscopy to determine the presence of aripiprazole. The synthesized dots were analyzed and characterized using transmission electron microscopy and Fourier transform infrared spectroscopy, and they showed a strong fluorescence emission peak at 475 nm. The proposed method was validated according to ICH M10 guidelines and was shown to be highly sensitive, allowing for nanoscale determination of aripiprazole in plasma matrix. Additionally, the method was compared to a previously reported spectrophotometric method, and it was found to be more sensitive and consistent with the principles of green analytical chemistry.

Guava-fruit based synthesis of carbon quantum dots for spectrofluorometric quantitative analysis of risperidone in spiked human plasma and pharmaceutical dosage forms.

Autism is one of the most pressing issues facing the international community in recent years, particularly in Middle Eastern countries. Risperidone is a selective serotonin type 2 and dopamine type 2 receptor antagonist. It is the most administered antipsychotic medication in children with autism-related behavioral disorders. Therapeutic monitoring of risperidone may improve safety and efficacy in autistic individuals. The main objective of this work was to develop a highly sensitive green fitted method for the determination of risperidone in the plasma matrix and pharmaceutical dosage forms. Novel water-soluble N-carbon quantum dots were synthesized from guava fruit, a natural green precursor, and used for determination of risperidone based on quenching fluorescence spectroscopy phenomena. The synthesized dots were characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The synthesized N-carbon quantum dots exhibited aquantum yield of 26.12% and showed a strong emission fluorescence peak at 475 nm when excited at 380 nm. The fluorescence intensity of the N-carbon quantum dots decreased with increasing risperidone concentration, indicating that the fluorescence quenching was concentration dependent. The presented method was carefully optimized and validated according to the guidelines of ICH, and it demonstrated good linearity in a concentration range of 5-150 ng mL-1. With a LOD of 1.379 ng mL-1 and a LOQ of 4.108 ng mL-1, the technique was extremely sensitive. Due to the high sensitivity of the proposed method, it could be effectively used for the determination of risperidone in the plasma matrix. The proposed method was compared with the previously reported HPLC method in terms of sensitivity and green chemistry metrics. The proposed method proved to be more sensitive and compatible with the principles of green analytical chemistry.

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels.

Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.

The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature.

Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a "Generally Recognized as Safe" substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.

Tectona grandis L.f: A comprehensive review on its patents, chemical constituents, and biological activities.

Tectona grandis L.f is a timber plant that is commonly referred to as teak. Its wide use as a medicine in the various indigenous systems makes it a plant of importance. A wide gamut of phytoconstituents like alkaloids, phenolic glycosides, steroids, etc. has been reported. A renewed interest in this plant has resulted in scientific investigations by various researchers towards the isolation and identification of active constituents along with scientific proof of its biological activities. The different parts of the plant have been scientifically evaluated for their antioxidant, antipyretic, analgesic, hypoglycemic, wound healing, cytotoxic, and many more biological activities. Documentation of this scientific knowledge is of importance to have consolidated precise information encompassing the various aspects of this plant, which could provide a base for future studies. This review is a compilation of the salient reports on these investigations concerning phytochemistry, the methods used to identify and quantify the constituents, the evaluation methods of the biological activity, toxicological studies, allergies and the patent/patent applications. This will further help researchers to find an area of the gap for future studies.

Synthesis and Development of a Novel First-in-Class Cofilin Inhibitor for Neuroinflammation in Hemorrhagic Brain Injury.

Intracerebral hemorrhage (ICH) is devastating among stroke types with high mortality. To date, not a single therapeutic intervention has been successful. Cofilin plays a critical role in inflammation and cell death. In the current study, we embarked on designing and synthesizing a first-in-class small-molecule inhibitor of cofilin to target secondary complications of ICH, mainly neuroinflammation. A series of compounds were synthesized, and two lead compounds SZ-3 and SK-1-32 were selected for further studies. Neuronal and microglial viabilities were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using neuroblastoma (SHSY-5Y) and human microglial (HMC-3) cell lines, respectively. Lipopolysaccharide (LPS)-induced inflammation in HMC-3 cells was used for neurotoxicity assay. Other assays include nitric oxide (NO) by Griess reagent, cofilin inhibition by F-actin depolymerization, migration by scratch wound assay, tumor necrosis factor (TNF-α) by enzyme-linked immunosorbent assay (ELISA), protease-activated receptor-1 (PAR-1) by immunocytochemistry and Western blotting (WB), and protein expression levels of several proteins by WB. SK-1-32 increased neuronal/microglial survival, reduced NO, and prevented neurotoxicity. However, SZ-3 showed no effect on neuronal/microglial survival but prevented microglia from LPS-induced inflammation by decreasing NO and preventing neurotoxicity. Therefore, we selected SZ-3 for further molecular studies, as it showed potent anti-inflammatory activities. SZ-3 decreased cofilin severing activity, and its treatment of LPS-activated HMC-3 cells attenuated microglial activation and suppressed migration and proliferation. HMC-3 cells subjected to thrombin, as an in vitro model for hemorrhagic stroke, and treated with SZ-3 after 3 h showed significantly decreased NO and TNF-α, significantly increased protein expression of phosphocofilin, and decreased PAR-1. In addition, SZ-3-treated SHSY-5Y showed a significant increase in cell viability by significantly reducing nuclear factor-κ B (NF-κB), caspase-3, and high-temperature requirement (HtrA2). Together, our results support the novel idea of targeting cofilin to counter neuroinflammation during secondary injury following ICH.

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19.

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.

Innovations and Patent Trends in the Development of USFDA Approved Protein Kinase Inhibitors in the Last Two Decades.

Protein kinase inhibitors (PKIs) are important therapeutic agents. As of 31 May 2021, the United States Food and Drug Administration (USFDA) has approved 70 PKIs. Most of the PKIs are employed to treat cancer and inflammatory diseases. Imatinib was the first PKI approved by USFDA in 2001. This review summarizes the compound patents and the essential polymorph patents of the PKIs approved by the USFDA from 2001 to 31 May 2021. The dates on the generic drug availability of the PKIs in the USA market have also been forecasted. It is expected that 19 and 48 PKIs will be genericized by 2025 and 2030, respectively, due to their compound patent expiry. This may reduce the financial toxicity associated with the existing PKIs. There are nearly 535 reported PKs. However, the USFDA approved PKIs target only about 10-15% of the total said PKs. As a result, there are still a large number of unexplored PKs. As the field advances during the next 20 years, one can anticipate that PKIs with many scaffolds, chemotypes, and pharmacophores will be developed.