Synthesis and Characterization of Dihydrouracil Analogs Utilizing Biginelli Hybrids

Dihydrouracil presents a crucial intermediate in the catabolism of uracil. The vital im-portance of uracil and its nucleoside, uridine, encourages scientists to synthesize novel dihydroura-cils. In this paper, we present an innovative, fast, and effective method for the synthesis of dihy-drouracils. Hence, under mild conditions, 3‐chloroperbenzoic acid was used to cleave the carbon– sulfur bond of the Biginelli hybrids 5,6‐dihydropyrimidin‐4(3H)‐ones. This approach led to thirteen novel dihydrouracils synthesized in moderate‐to‐high yields (32–99%)

Antileishmanial and antitrypanosomal activity of symmetrical dibenzyl-substituted α,β-unsaturated carbonyl-based compounds.

Human African Trypanosomiasis (HAT) and leishmaniasis are two of the most neglected challenging tropical diseases, caused by the kinetoplastid parasites and species, respectively. For both of these complex disease spectra, treatment options are limited and threatened by drug resistance, justifying urgent new drug discovery efforts. In the present study we investigated the antitrypanosomal and antileishmanial activity of a series of 21 symmetrical α,β-unsaturated carbonyl-based compounds, each featuring two 3-methoxybenzene attached to a central cyclohexanone, tetrahydro-4-pyranone scaffold or 4-piperidone ring. Structure-activity relationships were explored with respect to substitution on positions 3, 4 and 6 of the terminal 3-methoxybenzyl groups, and seven types of central ring. Compounds and , showed broad anti-kinetoplastid activity against all species and strains tested. Compound featuring -methyl-4-piperidone was found to be the most potent analog and therefore can serve as a potential lead for the development of new drug candidates for trypanosomiasis and leishmaniasis

Appraisal of acute oral toxicity of glucuronoxylan hydrogel from Mimosa pudica seeds

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits

Appraisal of acute oral toxicity of glucuronoxylan hydrogel from Mimosa pudica seeds

Glucuronoxylan hydrogel (GXH) isolated from M. pudica seeds was assessed for acute toxicology in albino mice that were alienated into four groups. Three groups, i.e., II, III and IV received GXH at a dose of 1, 2 and 5 g/kg, respectively while group I was retained untreated and provided routine diet. After administering GXH, mice were examined for vomiting, diarrhea, allergy and tremors for 8 h. All animals were carefully observed for food and water consumption at 1, 2, 3, 7 and 14 day after administering GXH. At the end of studies, blood samples were drawn for investigation of hematological and biochemical parameters. All animals were sacrificed, relative body weight of vital organs was calculated and their histopathology was studied. It was concluded that there was insignificant difference in body weight, behavioral pattern, food and water intake among treated and control groups. Haematology and biochemistry of blood samples from all groups were found analogous. Histopathological evaluation of vital body organs exhibited no lesions in all groups. Ocular, cardiac and dermal safety of GXH was also established on albino rabbits

Development of ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach

Development and evaluation of scaffold-based nanosponge formulation for controlled drug delivery of naproxen and ibuprofen

Purpose: To develop and evaluate nanosponge (NS) based sustained release formulations of naproxen (NAP) and ibuprofen (IBU).Method: Six formulations of each candidate drug were prepared by emulsion solvent diffusion method, using varying ratios of polymers, i.e., ethyl cellulose and polyvinyl alcohol. The prepared formulations were evaluated for various parameters including production yield, particle size, polydispersity index, actual drug content and entrapment efficiency. Morphological, structural and thermo-analytical evaluations were performed using various techniques. In vitro release studies were performed on selected formulations.Results: Nanosponge (NS) formulations of naproxen and ibuprofen were successfully prepared by emulsion solvent diffusion method. The particle size of naproxen and ibuprofen nanosponge formulations ranged from 347.6 to 1358 nm and 248.7 to 327.6 nm, respectively. Formulations with equal proportion of ethyl cellulose and drug resulted in nanosponges with the desired particle size. Production yield, actual drug content and entrapment efficiency was dependent on the ratio of ethyl cellulose and polyvinyl alcohol. Formulations with equal proportion showed least PDI values (0.09 for NAP and 0.07 for IBU) and highest zeta potential (-27.2 mV for NAP and -28.2 mV for IBU). Morphological, structural and thermo-analytical analysis confirmed the encapsulation of drugs in nanosponge cavities, and exhibited spherical and porous morphology. Nanosponge formulations gave a sustained release pattern, based on Higuchi model. Drug release mechanism was Fickian followed Korsmeyer-Peppas model, due probably to the porosity of the nanosponge.Conclusion: Sustained release nanosponge formulations of naproxen and ibuprofen have successfully been prepared.Keywords: Nanosponge, Naproxen, Ibuprofen, Emulsion solvent diffusion method, Sustained releas

Prospects of Artificial Intelligence in the Improvement of Healthcare Professions: A Review

In 1956, the development of engineering science led to the birth of the first intelligent machines. This has led to the term Artificial Intelligence (AI) coined by a scientist named John McCarthy. The basic purpose of AI is to minimise human cognitive function. Advanced computer technology allows humans to do comparative critical thinking and simulate intelligent behaviour by producing intelligent modelling to solve boost and uplift cracking problems, imaging knowledge, and making a decision.  Consequently, rapid analytical technique progress, powered by the increasing data availability in healthcare, has directed a paradigm shift in the healthcare system, especially in the analysis of medical imaging in the disease of oncology by detection of brain tumours. It helps the diagnosis of cancer stages based on the abnormal cell growth in the brain. AI is also important in diagnosis and treatment in other medical departments like dermatology, nephrology, ophthalmology, pathology, pulmonary medicine, endocrinology, gastroenterology, and neurology.  In recent years, AI has played a key role in pharmacy, drug delivery, drug discovery, drug formulation development, hospital pharmacy, and poly-pharmacology. The term AI has a broad range of applications in medicine, medical statistics, medical diagnosis, human biology, pharmacy, clinical, and robotics. Automated selective medication uses the scientific task approach of pharmacists and is only possible by the use of AI. Algorithmic tasks reserved by using AI automation and such type of AI demonstration are better than pharmacists in comparison. In general terms of AI, the minimal intervention of humans implies intelligent behaviour through computer models. The invention of robots is deemed the starting point of the AI journey. It started with the introduction of robotic biosynthetic machines utilised to support medical personnel. In the meantime, an AI is capable of analysing complex clinical and medical data where a potentially significant data set relationship can be used for treatment and predicting outcomes in the case study and diagnosis

Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties

A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity

Emerging Nanotherapeutic Approaches to Overcome Drug Resistance in Cancers with Update on Clinical Trials

A key issue with modern cancer treatments is the emergence of resistance to conventional chemotherapy and molecularly targeted medicines. Cancer nanotherapeutics were created in order to overcome the inherent limitations of traditional chemotherapeutics. Over the last few decades, cancer nanotherapeutics provided unparalleled opportunities to understand and overcome drug resistance through clinical assessment of rationally designed nanoparticulate delivery systems. In this context, various design strategies such as passive targeting, active targeting, nano-drug, and multimodal nano-drug combination therapy provided effective cancer treatment. Even though cancer nanotherapy has made great technological progress, tumor biology complexity and heterogeneity and a lack of comprehensive knowledge of nano-bio interactions remain important roadblocks to future clinical translation and commercialization. The current developments and advancements in cancer nanotherapeutics employing a wide variety of nanomaterial-based platforms to overcome cancer treatment resistance are discussed in this article. There is also a review of various nanotherapeutics-based approaches to cancer therapy, including targeting strategies for the tumor microenvironment and its components, advanced delivery systems for specific targeting of cancer stem cells (CSC), as well as exosomes for delivery strategies, and an update on clinical trials. Finally, challenges and the future perspective of the cancer nanotherapeutics to reverse cancer drug resistance are discussed