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.
Some novel non‐ulcerogenic N‐substitutedphenyl‐6‐oxo‐3‐phenylpyridazines as COX‐2 inhibitors have been developed (Supplementary material Appendix 1). The novel aldehyde 3 was prepared by reacting 6‐phenylpyridazin‐3(2H)‐one with 4‐fluorobenzaldehyde. The aldehyde 3 was reacted with different hydrazines and thiazolidin‐4‐ones to obtain the novel N‐substitutedphenyl‐6‐oxo‐3‐phenylpyridazine derivatives. These were assessed for their anti‐inflammatory potential and gastric ulcerogenic effects. The molecular docking investigations were also undertaken. The spectroscopic data were coherent with the allocated structures of the compounds. The compounds 4a (IC50 = 17.45 nm; p < .05), 4b (IC50 = 17.40 nm; p < .05), 5a (IC50 = 16.76 nm; p < .05), and 10 (IC50 = 17.15 nm; p < .05) displayed better COX‐2 inhibitory activity than celecoxib (IC50 = 17.79 nm; p < .05). These findings were consistent with the molecular docking investigations of 4a, 4b, 5a, and 10. The in vivo anti‐inflammatory profile of 4a, 4b, 5a, and 10 was also superior to celecoxib and indomethacin. The compounds 4b, 5a, and 10 revealed no gastric ulcerogenic effects, wherein the compound 4a produced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds 4a, 4b, 5a, and 10 have been postulated as promising non‐ulcerogenic COX‐2 inhibitors.
Cyclooxygenase-2 (COX-2) is implicated in the development of chronic inflammatory diseases. Recently, pyridazine derivatives have emerged as a novel prototype to develop COX-2 inhibitors. Accordingly, some pyridazine-based COX-2 inhibitors are reported herein. The reaction of aldehyde 3 and different hydrazines yielded the corresponding hydrazones. The hydrazones were further derivatized to the title compounds, which were assessed for COX-1 and COX-2 inhibitory action, gastric ulcerogenic effects, and lipid peroxidation properties. Molecular docking studies and determination of the physicochemical parameters were also carried out. The allocated structures of the reported compounds were coherent with their spectroscopic data. The compounds 9a (IC50 = 15.50 nM, 114.77%), 9b (IC50 = 17.50 nM, 101.65%), 12 (IC50 = 17.10 nM, 104.03%), 16b (IC50 = 16.90 nM, 105.26%), and 17 (IC50 = 17.70 nM, 100.5%) displayed better COX-2 inhibition than celecoxib (IC50 = 17.79 nM, 100%). These outcomes were harmonious with the molecular docking studies of 9a, 9b, 12, 16b, and 17. These compounds also displayed comparable onset and the duration of action concerning celecoxib and indomethacin in the in vivo studies. No ulcerogenic effects were observed for 9a and 12, whereas 9b, 16b, and 17 showed an insignificant ulcerogenic effect compared to celecoxib. The compounds 9a, 9b, 12, 16b, and 17 displayed a better lipid peroxidation profile than celecoxib and indomethacin. The compounds 9a (%ABS = 84.09), 9b (%ABS = 84.09), 12 (%ABS = 66.87), 16b (%ABS = 75.02), and 17 (%ABS = 81.42) also displayed appreciable calculated absorption compared to celecoxib (%ABS = 82.09). The compounds 9a, 9b, 11, 16b, and 17 have been recognized and postulated as non-ulcerogenic COX-2 inhibitors with promising physicochemical parameters and gastric safety profile. These compounds may be useful candidates to combat diseases caused by higher levels of COX-2.
: Leishmaniasis is one of the six entities on the list of most important diseases of the World Health Organization/Tropical Disease Research (WHO/TDR). After Malaria, it is one of the most prevalent and lethal parasitic diseases. VL is one of the most fatal forms of this disease, especially if left untreated. The drugs that are currently available for the treatment of this disease are expensive, toxic or no longer effective especially in endemic regions. Currently no vaccine has been developed to immunize humans against this disease. The major problems with the current drugs are the development of resistance and their adverse effects. Therefore, there is a strong urge to research and design drugs that have better efficacies and low toxicities as compared to current chemotherapy drugs. Leishmania has various enzymes involved in its metabolic pathways which are unique to either the same genus or trypanosomatids making them a very suitable, attractive and novel target sites for drug development. One of the major pathways unique to trypanosomatids is the thiol metabolism pathway which in involved in the maintenance of redox homeostasis as well as protection of the parasite in the macrophage from oxidative stress induced damage. Herein several pathways and their enzyme systems have been discussed as well as the proposed changes in the parasite due to drug resistance to help to determine the most suitable drug target. The thiol metabolism pathway is discussed in extensive detail providing evidence of this pathway being the most favorable choice for drug targeting.
Niosomal drug delivery system serves as drug depots within the body that release the drug in a controlled manner through its bilayer, providing the enclosed drug to be released with sustainedaction.Transdermal drug delivery system for steroidal drug molecules through the development of a niosomal gel is needed for an optimized drug delivery system due to various problems associated with conventional treatment of steroidal molecule. The objective of this study was to develop a niosomalgel-based formulation system for testosterone steroidal molecule dissolved in a mixture of non-ionic surfactant and cholesterol in nanoparticulate form and evaluation of niosomal gel by different optimization parameters. The niosomal gel dispersion was prepared by heating system technique.The drug loaded niosomes showed much less vesicle size [10-500 nm] and good PDI, which means that the drug loaded can easily permeate the skin. Niosomal based gel was formulated by using the xanthan gum as gelling agent by optimizing different concentration of different gelling agents to get the best consistency of final niosomal gel. Various measurement parameters such as product quality, pH, purity, homogeneity, spread ability, viscosity, In vitro drug release, particle size determination, zeta potential, FTIR studies and TEM analysis were done to optimize the best batch.Entrapment efficiency was very good with value of 92.17 ± 0.02 percent. Niosomal gel has been found to exhibit strong consistency, good homogeneity, spread ability, and viscosity parameters.Studies of FTIR showed no excipient interaction with the API molecule. TEM images showed that all the particles were in uniform range in niosomal dispersion.Data on the release of in vitro drugs also showed that the release pattern was comparable to the industry formula. The niosomalbased gel formulation developed can be a promising alternative to delivering steroidalbased molecule to minimize the side effects due to skin problems as well as to increase the permeation rate of steroids by using transdermal drug delivery.
Objective: The objective of present study was formulation development of imiquimod using lactic acid and span 80 for topical delivery to cure genital warts.Methods: Lipid based vesicles (LBV) of 2% imiquimod were prepared with phospholipoin 90G, ethanol, lactic acid and span 80 using central composite design. The prepared vesicles were optimized statistically and characterized for particle size, zeta potential, percentage entrapment efficiency (% EE) and transmission electron microscopy (TEM). The optimized LBV were incorporated into gel formulation which was evaluated and compared with control gel and marketed formulation.Results: The optimized vesicles had particle size 394.8±9.6 nm, zeta potential-16.5±2.5 mV, % EE 88.27±0.45 and TEM study confirmed the formation of vesicular structure with spherical shape. The gel formulation of imiquimod vesicles showed positive results like spreadability 14.3±0.34 gcm/s, viscosity 13500±1.67 cp, consistency 6.1±0.14 mm and extrudability 16.47±0.11 g/cm 2Conclusion: Results of in vitro and in vivo studies indicated that this vesicle gel formulation provided efficient and site specific dermal delivery of imiquimod for cure of genital warts.. In vitro permeation amount of drug was remarkably lower (10.13 %) than control (87.17 %) and marketed formulation (27.46 %). Results of retained drug for both in vitro as well as in vivo permeation study and local accumulation efficiency (4.021±0.2292) were considerably higher for LBV gel than control (0.1008±0.002513) and marketed formulation (0.8314±0.0300). To understand the mechanism of interaction between skin and vesicles, fourier transform infra-red spectroscopy studies were also done. Results of skin irritancy test and histological examination revealed biocompatible nature of formulation.
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