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In this study, newly synthesized 20 nitroimidazole derivatives were subjected to 2D and 3D Quantitative Structure-Activity Relationship (QSAR) study to investigate their anti-HIV activity against both ROD and IIIB strains. Later, proposed hypothesis was virtually proved by further in-silico studies. In statistically significant 2D-QSAR models r2 values for IIIB strains 0.9241 and for ROD strains 0.9412 with corresponding q2 values of 0.7706 and 0.8299, were obtained, respectively. Different models were constructed using three different kNN-MFA 3D QSAR approaches such as SW-FB, SA score, and GA. By using the generated hypothesis, newer analogues of nitroimidazole derivatives was designed and molecular modelling studies were conducted to prove the hypothesis. The three molecules were displayed the good docking scores compared to the reference molecule. The stabilities of docked complexes were analyzed by MD simulations and MMGB/SA calculations. These results offer insightful design guidance for novel anti-HIV compounds synthesis and suggest interesting directions for future pharmaceutical research.

Diabetes is a prevalent disease in South India, posing a severe threat to public health. To tackle this issue, researchers are focusing on developing multi-targeted ligands, and one promising candidate is (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (DMDA). Geometry optimization of DMDA was carried out using density functional theory with 6–311+G(d, p) basis set to develop a theoretical model close to the previously synthesized and reported DMDA. Natural Bond Orbital analysis was conducted to scrutinize the phenomena of charge delocalization and electronic exchange interactions governing both intermolecular and intramolecular associations. Moreover, the vibrational characteristics of the molecule were elucidated through FT-IR and FT-Raman spectra. Lowest Unoccupied Molecular Orbital and Highest Occupied Molecular Orbital have also been explored to enhance understanding of the molecule's electronic structure and reactivity. Hirshfeld surface analysis was utilized to investigate the interactions between molecules within the crystalline lattice. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis elucidates the potential pharmacokinetic profile of DMDA. Molecular docking was performed to predict the binding site responsible for various interactions with the targeted protein. By combining these techniques, a comprehensive molecular description of DMDA has been generated.There are three prominent intramolecular interactions within the ambit of van der Waals radii, leading to stability of the molecule. The presence of a broad and shallow band with a significant red shift provides evidence for the strong intermolecular OH hydrogen bonding. DMDA complies with Lipinski's Rule of Five, highlighting its favorable characteristics for pharmaceutical efficacy. The negative binding energies determined by docking studies ascertain the potential sites of ligand-protein interaction leading to inhibition of α-amylase and α-glucosidase enzyme.

Rheumatoid arthritis (RA) is an autoimmune disease that causes distinctive inflammatory symptoms and affects over 21 million people worldwide. RA is characterized by severe discomfort, swelling, and degradation of the bone and cartilage, further impairing joint function. The current study investigates the antiarthritic effect of a methanolic extract of Artemisia pallens (methanolic extract of A. pallens, MEAP), an aromatic herb. Artemisinin content (% per dry weight of the plant) was estimated using a UV Vis spectrophotometer. In the present study, animals were divided into six groups (n = 6). The control group (group I) was injected with 0.25% of carboxymethyl cellulose. The arthritic control group (group II) was treated with Freund’s complete adjuvant (by injecting 0.1 mL). Prednisolone (10 mg/kg), a lower dose of MEAP (100 mg/kg), a medium dose of MEAP (200 mg/kg), and a higher dose of MEAP (400 mg/kg) were orally delivered to groups III, IV, V, and VI, respectively. Freund’s complete adjuvant was administered into the sub-plantar portion of the left-hind paw in all the groups except vehicle control to induce rheumatoid arthritis. Weight variation; joint diameter; paw volume; thermal and mechanical hyperalgesia; hematological, biochemical, and oxidative stress parameters; radiology; and a histopathological assessment of the synovial joint were observed in order to evaluate the antiarthritic effect of the methanolic extract of A. pallens. In this study, the estimated content of artemisinin was found to be 0.28% (per dry weight of the plant), which was in good agreement with the reported value. MEAP (200 and 400 mg/kg) caused a significant reduction in increased paw volume and joint diameter in arthritic rats while significantly increasing body weight and the mechanical threshold of thermal algesia. Moreover, complete blood counts and serum enzyme levels improved significantly. Radiological analysis showed a reduction in soft tissue swelling and small erosions. A histopathological examination of the cells revealed reduced cell infiltration and the erosion of joint cartilage in MEAP-administered arthritic rats. The present research suggests that the antiarthritic activity of the methanolic extract of A. pallens wall is promising, as evidenced by the findings explored in our rat model.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of −8.35, −9.67 and −8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski’s rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

Deep eutectic solvents (DESs) are a class of ionic liquid analogues that have received heightened research attention in recent years. These binary or ternary mixtures are composed of quaternary salts, metal salts, or organic compounds that exhibit hydrogen bond donating and accepting behaviours within the DES system, forming a hydrogen bond network that results in melting point depression. The facile preparation of DESs coupled with the virtually unlimited combination of components enables a large number of unique solvents to be produced, characterized, and applied; accordingly, highly tailorable agents can be prepared for specific applications. Numerous applied studies have utilized DESs; however, current fundamental knowledge of DES physicochemical and phase equilibria properties is relatively limited compared to the wide spectrum of possible formulations. Furthermore, available reporting of DES physicochemical properties encompasses a multitude of parameters, from density and ionic conductivity to more niche properties such as vapour pressure and acoustic properties. Therefore, a comprehensive review that compiles and evaluates recent works documenting the physicochemical properties of DESs is required to improve our understanding of fundamental DES properties and their prospective applications, and to identify gaps in this critical research area. Accordingly, this paper aims to act as a reference on the physicochemical properties of DESs and illuminate efforts dedicated to this foundational research area.

A series of phthalimide-capped benzene sulphonamides (1–22) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds 1, 3, 10, and 15 showed hCA I inhibition, whereas 1, 4, and 10 showed hCA II inhibition at nanomolar concentrations. Among these compounds, 1 displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound 1 towards hCA II.

Cancer is the most challenging global health issue despite advancement in new drug development and biological understanding of oncology. Metastasis is the hallmark of cancer development resulting in huge death and it remained poorly understood. Various research articles published to control cancer and metastasis using lipidic nanocarriers so far. However, safety and high patient compliance are the prime concern. Medication is always of major concern for a clinician before prescribing any dosage form or drug. The high toxicity profile of anticancer drugs led to increased financial burden of treatment, mortality and complex consequences. Therefore, conventional dosage forms failed to culminate various issues related to therapeutic efficacy and drug related toxicity. Then, many researchers tried the novel drug delivery systems for effective and safe targeting of anticancer drugs. Exosomes, vesicular systems, and erythrocytes have been explored to treat cancer. It was imperative to compile major findings from these researches carried out so far. In the review, we highlighted application of exosomes, liposomes, and erythrocytes to control metastasis and cancer. Moreover, we have addressed various critical attributes of liposomes while formulation design for improved therapeutic efficacy and mechanistic perspective for drug targeting using the described vesicular carriers. Finally, we compiled major findings of clinical data published in clinical research plate-form. This review highlighted the major findings associated with nanovesicles based tumor targeting in which anticancer drugs are encapsulated in suitable vesicular systems and reach to site specific delivery of drugs.

Cancer is still a global challenge for healthcare professional and scientists due to complicated pathological pathways, inefficient early diagnosis, and limited safe delivery system at economic treatment cost. Despite these, other factors (life style, environmental problem, socio-economic issues, patient related complications, expensive therapy, and genetic history of oncogene) played significant role to spread and complicate treatment. However, various novel carriers have been explored and reported for effective and efficient drug delivery using polymers and lipid. Among them, vesicular systems are considered as the most biocompatible and safe for delivery of hydrophilic and lipophilic drug candidates. Therefore, the present review addressed various forms of nanovesicular systems with their benefits, progressive development stages, and mechanistic insights for drug targeting (active and passive), specific cancer wise nanovesicles, exosomes, and commercial products with potential clinical applications. The review primarily highlighted the major findings of nanovesicles employed to control solid tumor when a chemotherapeutic drug was used in specific vesicles based nanocarriers. Notably, miscellaneous exosomes, blood cells-based drug delivery (neutrophils and leukocytes), pH-responsive nanovesicles improved drug therapy by targeting tumor tissues and high drug access in the site of action. Finally, co-administration of chemotherapeutic drugs (combination therapy) further revealed convincing therapeutic outcomes as compared to standalone.

Rheumatoid arthritis (RA) is an autoimmune disease that causes distinctive inflammatory symptoms and affects over 21 million people worldwide. RA is characterized by severe discomfort, swelling, and degradation of the bone and cartilage, further impairing joint function. The current study investigates the antiarthritic effect of a methanolic extract of Artemisia pallens (methanolic extract of A. pallens, MEAP), an aromatic herb. Artemisinin content (% per dry weight of the plant) was estimated using a UV Vis spectrophotometer. In the present study, animals were divided into six groups (n = 6). The control group (group I) was injected with 0.25% of carboxymethyl cellulose. The arthritic control group (group II) was treated with Freund's complete adjuvant (by injecting 0.1 mL). Prednisolone (10 mg/kg), a lower dose of MEAP (100 mg/kg), a medium dose of MEAP (200 mg/kg), and a higher dose of MEAP (400 mg/kg) were orally delivered to groups III, IV, V, and VI, respectively. Freund's complete adjuvant was administered into the sub-plantar portion of the left-hind paw in all the groups except vehicle control to induce rheumatoid arthritis. Weight variation; joint diameter; paw volume; thermal and mechanical hyperalgesia; hematological, biochemical, and oxidative stress parameters; radiology; and a histopathological assessment of the synovial joint were observed in order to evaluate the antiarthritic effect of the methanolic extract of A. pallens. In this study, the estimated content of artemisinin was found to be 0.28% (per dry weight of the plant), which was in good agreement with the reported value. MEAP (200 and 400 mg/kg) caused a significant reduction in increased paw volume and joint diameter in arthritic rats while significantly increasing body weight and the mechanical threshold of thermal algesia. Moreover, complete blood counts and serum enzyme levels improved significantly. Radiological analysis showed a reduction in soft tissue swelling and small erosions. A histopathological examination of the cells revealed reduced cell infiltration and the erosion of joint cartilage in MEAP-administered arthritic rats. The present research suggests that the antiarthritic activity of the methanolic extract of A. pallens wall is promising, as evidenced by the findings explored in our rat model. [ABSTRACT FROM AUTHOR]

A new approach was applied for the development of a precise, simple, and economic analytical process for the accurate analysis of tolterodine tartrate (TOT) in its bulk and tablet using HSPiP- and quality by design (QbD)-assisted methods. The HSPiP program predicted several solvents and their right ratios for the mobile phase, followed by simulating the experimental solubility data in various predicted solvents. QbD was used to identify the impact of the composition and the mobile phase flow rate on the peak area and retention time. TOT was estimated using an Agilent TC C18 column employing an optimized mobile phase. The HSPiP shortened the solvent selection time with high reliability, whereas QbD identified critical factors. The optimized composition and process variables were used to develop an analytical method for TOT estimation. Various analytical validation parameters were estimated with constructed linearity of 5–30 μg/mL and a percent recovery yield value of 100.36%. To ensure the reliability of the optimized method, we estimated validation parameters (linearity, specificity, precision, accuracy, robustness, and ruggedness) to comply with the ICH guidelines. Considering the high recovery yield, good regression coefficient, low detection limit, and low noise ratio, the optimized method was accurate and precise with a high degree of specificity, rapid process, and reproducibility for the quantitative estimation of tolterodine from both oral analytes (I and II). The validated method was implemented for pharmacokinetic study in rats for quantitative estimation of the analytes with high accuracy, sensitivity, and reproducibility. [ABSTRACT FROM AUTHOR]

Water purification from brackish water sources has been acknowledged as one of the most promising ways to produce drinkable water in water-scarce areas. In this study, an ultra-low pressure reverse osmosis (ULPRO) membrane was numerically and experimentally investigated to produce drinking water by the removal of sodium chloride salt which provides further validation of the model from a practical perspective. An enhanced predictive model based on the Donnan–Steric Pore Model with dielectric exclusion (DSPM-DE) incorporating the osmotic effects was formulated in process simulation. The feed pressure and concentration were optimized as input variables and interaction between them was observed, while salt rejection and water recovery rate were taken as response attributes. The results obtained on the ULPRO membrane showed that the performance depends on the charge, steric, and dielectric effects. Furthermore, the enhanced model was validated with the experimental data attained from a laboratory-scale filtration system with good accuracy in the salt rejection and water recovery results. Comparing the enhanced DSPM-DE with the existing solution diffusion model reveals that the enhanced model predicts the membrane performance better and thereby qualifies itself as a reliable model for desalination of brackish water using ULPRO membrane. HIGHLIGHTS An enhanced DSPM with a dielectric exclusion model for ULPRO membrane is developed.; Predicted ULPRO membrane performance for low operating pressure of 1 to 4 bar.; Predicted ULPRO membrane performance for brackish water at salinity up to 2,000 ppm.; Model validated through experimental data for salt rejection and water recovery with good accuracy.; Enhanced model predicts salt rejection better than using solution diffusion model.;

Employing low quality feedstocks for biodiesel production can present cost reduction opportunities due to its wide availability and cost effectiveness. However, most low quality feedstocks have high free fatty acid (FFA) content which is not feasible for biodiesel production through direct transesterification due to soap formation. Thus, a pre-treatment step through FFA esterification could reduce the FFA content while simultaneously yielding fatty acid methyl esters (FAME). In this study, the catalytic activity of ten ionic liquids (ILs) were screened for the esterification of FFA in acidic crude palm oil (ACPO). 1‑butyl‑3-methylimidazolium hydrogen sulfate as IL exhibited the highest catalytic activity and was further investigated to determine the optimum operating parameters such as IL dosage, molar ratio, reaction temperature and time. Single factor optimization was employed for the laboratory scale batch esterification reaction. The FFA content was reduced from 10.77% to less than 1% using the following optimum conditions: 4% IL to oil, molar ratio of 10:1 (methanol to oil), 120 min reaction time and 60 °C reaction temperature. Under optimum conditions, the IL can be recycled five times with minimal loss in catalytic activity, highlighting its feasibility as an industrial catalyst for esterification of acidic oils and fats.