Human dihydroorotate dehydrogenase (hDHODH) is a rate-limiting enzyme in the de novo pyrimidine biosynthesis pathway that catalyses the oxidation of dihydroorotate to orotate and represents an attractive target for anticancer therapy. In this study, Gaussian-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed to design two series comprising 102 novel thiadiazole-based hDHODH inhibitors. Combined in silico approaches, including molecular docking, binding free energy calculations, and molecular dynamics (MD) simulations, were employed to further optimised designed compounds for synthesis. Based on these analyses, 35 designed compounds were synthesized and characterized using standard analytical techniques. In vitro hDHODH enzyme inhibition and MTT assays revealed that compounds 31 and 46 exhibited the highest inhibitory activity against hDHODH and showed potent antiproliferative effects against A-375 melanoma and KB-3-1 cell lines, while displaying no cytotoxicity toward non-cancerous Vero cells. Scratch assay demonstrated that compounds 24, 31, 46, and 50 significantly inhibited cancer cell migration. In vivo evaluation using a DMBA-induced skin cancer model in Swiss albino mice showed that several compounds significantly reduced tumor nodules and proliferative lesions, improved survival rates, and decreased DHODH levels. Overall, compound 31 emerged as the most potent hDHODH inhibitor and a promising lead for anticancer drug development.

Imidazo based heterocyclic derivatives are considered as privileged scaffolds due to their presence in various pharmacologically active compounds and in marketed formulations. The present study reports toxicological evaluation of three imidazo based heterocyclic derivatives which are currently being investigated for their potential anticancer activity. Compounds IG-01–007, IG-01–008, and IG-01–009 were assessed for cytotoxicity, hemolysis, and DNA fragmentation activity. Acute oral toxicity studies were performed at doses of 300 mg/kg and 1000 mg/kg according to OECD guidelines, in both male and female Wistar rats. All test compounds at a concentration of 50 µM resulted in DNA fragmentation suggesting notable impact on DNA integrity. The in-vivo acute toxicity study indicated significant toxicity at doses of ≥ 1000 mg/kg, particularly for compounds IG-01–008 and IG-01–009, which caused hepatic damage and cholestasis in liver tissues. These results collectively suggest that imidazo based heterocyclic derivatives used in the present study exhibit cytotoxic potential.

Hydrazone chemistry has become important and plays a key role in the development of organic compounds. Hydrazones can be useful pharmacophores for creating novel derivatives, owing to their broad range of activities. In this study, a series of N-((2-hydroxy-3-(2-(substitutedbenzylidene)hydrazine-1-carbonyl)naphthalen-1-yl)(3-nitro-phenyl/3,4-dimethoxyphenyl)methyl)acetamide derivatives were prepared, characterized by FTIR, 1H-NMR, 13C-NMR, and mass spectroscopy, and evaluated for their antimicrobial, antiinflammatory, and antioxidant activities along with in silico studies. The substituted derivatives were synthesized by the reaction of acetonitrile, chlorosulphonic acid, and substituted benzaldehyde with the hydrazones. The antimicrobial evaluation showed that compound 3i had more antimicrobial potential than the other tested molecules. Compound 3j had more antioxidant potential than the other synthesized compounds. Two compounds, 3f and 3h, had better antiinflammatory activity. The binding affinities of synthesized derivatives into the active sites of receptor proteins were characterized by utilizing the advanced docking program AutoDock Vina. In silico ADMET studies were performed using Molinspiration, pre-ADMET, and OSIRIS property explorer for the prediction of pharmacokinetic behavior of synthesized compounds.

Lung cancer is the second deadliest disease in the world. A major portion of deaths related to cancer are due to lung cancer in both males and females. Interestingly, unbelievable advances have occurred in recent years through the use of nanotechnology and development in both the diagnosis and treatment of lung cancer. Due to their in vivo stability, the nanotechnology-based pharmacological system gained huge attractiveness, solubility, absorption from the intestine, pharmacological effectiveness, etc. of various anticancer agents. However, this field needs to be utilized more to get maximum results in the treatment of lung cancer, along with wider context medicines. In the present review, authors have tried to concentrate their attention on lung cancer`s difficulties along with the current pharmacological and diagnostic situation, and current advancements in approaches based on nanotechnology for the treatment and diagnosis of lung cancer. While nanotechnology offers these promising avenues for lung cancer diagnosis and treatment, it is important to acknowledge the need for careful evaluation of safety, efficacy, and regulatory approval. With continued research and development, nanotechnology holds tremendous potential to revolutionize the management of lung cancer and improve patient outcomes. The review also highlights the involvement of endocrine systems, especially estrogen in lung cancer proliferation. Some of the recent clinical trials and patents on nanoparticle-based formulations that have applications in the treatment and diagnosis of lung cancer are also discussed.

Starch derived from plants plays an essential role in pharmaceuticals due to its components Amylose and Amylopectin, which form essential granules for drug delivery. Its biocompatibility and cost-effectiveness make it indispensable in pharmaceutical formulations, facilitating controlled drug release and tablet breakdown. The effectiveness and safety of drug formulations are often hindered by challenges such as low solubility and stability. In order to overcome these obstacles, current research is focused on modifying the properties of starch. The goal is to improve its solubility, swelling, erosion, stability, and ability to release drugs. A promising solution that has emerged is ultrasound-based modification. This technique has shown great potential in transforming starch granules, leading to improved solubility, degradability, and control over drug release. Not only is this method efficient and quick, but it also has the added benefit of being eco-friendly. This discussion will explore the mechanisms behind the modification of starch based on ultrasound, delving into both the physical and chemical changes that occur in starch granules. The analysis explores the utilization of modified starch induced by ultrasound in the field of drug delivery, investigating its stability and compatibility with biological systems. By exploring the capabilities and difficulties associated with the use of ultrasound to change starch for the delivery of drugs, we highlighted its potential as a leading and effective methodology.

Mammary gland carcinoma is one of the most prevalent and deadly diseases among women globally. It is a type of solid malignant tumor. In this malignant tumor, the microenvironment becomes hypoxic in rapidly proliferating cancer cells. These cells undergo adaptive changes through the expression of hypoxia-inducible factor-1alpha (HIF-1 alpha) which is regulated by factor inhibiting HIF-1 alpha (FIH-1). Considering this, we hypothesized that the chemical activation of FIH-1 would inhibit the hypoxic activity of HIF-1 alpha in mammary gland carcinoma. A library of 67,609 chemical compounds was virtually screened against FIH-1 based on Lipinski's rule from the ZINC database. The BBAP-8 has been selected based on an excellent docking score (-8.352 Kcal/mol), favorable ADMET, and potential FIH-1 activator profile. Further, its in-vitro cytotoxicity and apoptotic activity were scrutinized against MCF-7 cells and in-vivo activity against 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland carcinoma in Wistar rats. It exhibited significant cytotoxicity (IC50 = 16.59 +/- 0.49 mu M) and activated apoptosis when scrutinized through DAPI, AO/EB, and JC-1 staining. Also, oral administration of BBAP-8 restored hemodynamic changes, normalized tissue architecture, and corrected metabolic abnormalities. The western blot analysis and mRNA expression analysis validated that BBAP-8 has the potential to activate FIH-1 with the downregulation of GLUT-1, VEGF, and Twist-1. Moreover, BBAP-8 fostered apoptosis, when evaluated through BCL-2, BAX, Caspase-8, and Caspase-3. Based on research findings, this implies that BBAP-8 activates FIH-1 and can be effective in chemotherapeutic treatment of mammary gland carcinoma. The present study aimed to assess the role of chemical activation of Factor inhibiting HIF-1 alpha (FIH-1) in the regulation of hypoxia in fastly growing tumor cells. A library of 67,609 chemical compounds was virtually screened and BBAP-8 showed an excellent anticancer potential. image

Spices are utilized for both culinary and medicinal purposes and have been for a very long time originating from Sri Lanka and southern India, Cinnamomum verum may also be found in other Asian, Caribbean, Australian, and African countries. The principal compounds contained are Cinnamaldehyde and Eugenol, both of which have unique medicinal qualities in the leaves of Cinnamomum verum. Cinnamonaldehyde (CA), a bioactive phytochemical offer therapeutic advantages against the beginning of cardiovascular illnesses. Eugenol is an organic compound found in the leaves of Cinnamomum verum. Eugenol has antihypercholesterolemic and antiatherogenic effects. Eugenol's smooth muscle relaxant effect is due to its inhibition of receptor-operated and voltage-sensitive channels. Endothelial cells create nitric oxide (NO), which relaxes blood vessels. Eugenol has substantial anti-inflammatory properties. The antipyretic activity of eugenol is well recognized, since it reduces fever by reducing prostaglandin and sodium archidonate synthesis. Eugenol's hydrophobic nature allows it to pass the blood-brain barrier and enter the brain. Eugenol protects neuronal cells against the oxidative and excitotoxic effects of N-methyl-D-aspartate (NDMA). Eugenol has neuroprotective properties in hippocampal tissues due to its capacity to reduce brain-derived neurotrophic factor (BDNF) and postpone amyloid β -peptide (A- β) induced cell death via abnormal Ca2+ blocking. Anti-hypertensive property of Eugenol is known as it has the ability to activate TRPV channels and to relax endothelium-depleted arteries. Eugenol, which is found in Cinnamomum verum leaves, has been shown to be beneficial in the control of hypertension and so may be beneficial in the management of vascular dementia.

Linseed (Linum usitatissimum) is a versatile crop cultivated for its seeds, which are valuable source of ω-3 fatty acids. It adversely affected by soil salinity, as high salt levels can hinder their growth and reduce yields. To assess the potential for mitigating the adverse effects of high salinity concentrations, enhancing the resilience of three genotypes (Shekhar, Sheela, and Kartika) of linseed plants, this research aimed to find out the impact of Gibberellic acid (GA3) and Calcium (Ca) on various aspects of root morphology, osmotic potential of linseed, under varying levels of Cl- dominated salinity. The study employed three salinity levels (0, 5, and 10 dSm-1) and exogenous application of 10−6 M GA3 and/or 10 mg CaCl2 kg-1 in potted plants.The findings indicated that increasing salinity stress significantly (p≤0.05) affected root parameters, including total surface area(43.45%), average diameter(42.06%), total projected area(44.45%), length per volume (66.23%), root length, total root volume (73.23%), tips, forks,fine roots, and osmotic potential(66.67%). Correlations among linseed genotypes were observed between various root morphology and osmotic potential parameters. The application of GA3 and Ca effectively ameliorated the impact of salinity stress at its highest level (10 dSm-1), resulting in increased root parameters while decreasing the osmotic potential (Ψs). Both GA3 and Ca treatments significantly influenced root architecture and maintained optimal osmotic potential. The chloride-dominated salinity exerted inhibitory effects on all three genotypes’ (Shekhar, Sheela, and Kartika) root growth parameters while applying GA3 and Ca successfully mitigated these effects, enhancing root growth.

This study involves the design of novel thiadiazole derivatives as hDHODH inhibitors using various structure-based approaches such as pharmacophore modelling, high-throughput virtual screening (HTVS), prediction of ADMET parameters, docking and molecular dynamics (MD) studies. We used the validated co-crystal structure of hDHODH to create the six-feature pharmacophore model ADHRRR, which was validated by the Guner-Henry scoring (GH score=0.81) approach, enrichment calculations (enrichment factor=51), area under the curve (0.93), receiving operating characteristic (ROC) curve (0.89), and ROC ' s Boltzmann-enhanced discrimination, known as BEDROC (alpha=8) (0.859), (alpha=20) (0.828), (alpha=160) (0.912). Pharmacophore model as a 3D search query was used for the screening of zinc database followed by docking investigations and energy calculation (Prime/MMGBSA). For the design of novel compounds, we selected the thiadiazole moiety as the central scaffold and various functional groups based on pharmacophoric characters and binding interactions. In docking study, designed compounds showed favourable interactions with Gln47 and Arg136 at the active site of the hDHODH enzyme, and optimal drug likeness properties for ADMET prediction study. Stability of enzyme-ligand complex was validated by MD simulation study with RMSD, RMSF and RoG calculations. These findings suggested that novel thiadiazoles are potential candidates as hDHODH inhibitors and anticancer agents. In this work, structure-based computational design strategies, mainly structure-based pharmacophore modelling, virtual screening, molecular docking, ADMET prediction, and molecular dynamic (MD) simulations, along with their validation, are performed for the design of novel thiadiazole derivatives as hDHODH inhibitors. Designed compounds 8d and 2d demonstrated good potential for their future development as selective hDHODH inhibitors and anticancer agents. image

Sugarcane has a historical use in the treatment of various conditions, including jaundice, hemorrhage, urinary disorders, gastrointestinal disturbances, and ocular diseases. The plant is also recognized for its cardiotonic, diuretic, and laxative properties. It exhibits anti-inflammatory, antimicrobial, anti-ulcerative, and antioxidant activities. Policosanol, a key constituent, is known to lower cholesterol levels by inhibiting HMG-CoA reductase, a critical enzyme in cholesterol biosynthesis. Diabetes mellitus is a metabolic disorder characterized by the body's inability to effectively regulate blood glucose levels. The pancreas, normally responsible for insulin production, fails to produce sufficient quantities or the body develops insulin resistance. This leads to hyperglycemia. Fatty acids contribute to an increase in diacylglycerol, triglycerides, ceramides, and reactive oxygen species, ultimately leading to mitochondrial dysfunction, endoplasmic reticulum stress, and impaired autophagy. These factors contribute to beta-cell dysfunction and death, culminating in the development of type 2 diabetes. Given the cholesterol-lowering properties of policosanol, sugarcane leaves may offer potential benefits in management of type 2 diabetes.

Delivery of therapeutics using synthetic polymers is challenging due to toxicity, immunogenicity and impaired bioavailability following administration. However, natural polymers are being explored as safe for their use as a substitute for synthetic polymers. In the past three decades, the biomaterials like starches have been applied to impart an imperative role in delivering therapeutics. There is an increased focus on finding new sources of starches and their modifications. Hence, the derivatization of starches has become necessary to achieve desired properties. The modifications to native starch systems are being investigated to improve solubility, stability, bioavailability, etc., of an incorporated drug(s) and lower-down induced toxicities. All these requirements have led to the use of modified starches in the drug delivery of bioactive component(s). This review explores the current state of knowledge about starch structure and chemical modification methods from perspectives. It integrates aspects of its use in developing drug delivery devices like tablets, hydrogel, and patches. The information provided in this review may be applied as a reference for future chemically modified starch as excipients in drug carrier studies.

The chemical modifications of starch granules have been adopted to improve the characteristics, viz., paste clarity, resistant starch content, thermal stability, and so forth. The modified starch has been applied as a biopolymer in developing various preparations of food, nutraceutical, and pharmaceutical importance. The present work is focused on phosphorylation of alkali extracted mandua starch for improving digestion resistibility. The phosphorylation of mandua starch extracted from grains of Eleusine coracana (family Poaceae) was carried out by sodium tripolyphosphate/sodium trimetaphosphate at alkaline pH. After chemical treatment of mandua starch, the resistant starch (RS) content was increased significantly. The digestibility of chemically modified starch (CMS) was decreased down after treating by the phosphorylation process. The digestibility of CMS and alkali extracted mandua starch (AMS) in simulated intestinal fluid was found to be 32.64 ± 1.98% w/w and 61.12 ± 2.54% w/w, respectively. After chemical modification of mandua starch, a decrement was observed in amylose content, water-binding capacity, and swelling power. In the three-stage decomposition pattern of CMS studied by thermal gravimetric analysis, the significant changes in decomposition behavior also affirmed the impact of cross-linking in the improvement of stability of internal structure and resistibility of starch. In Fourier transform infrared (FTIR), the formation of the P=O bond was observed in CMS at 1250 cm–1. The acute and sub-acute toxicity studies in terms of behavioral, haematological, and enzymological parameters for CMS were not different significantly from AMS and control (p > 0.05). The cellular architecture of the liver and the kidney were found normal after consumption of CMS. The results revealed that significant increment in RS fraction occurred after cross-linking of mandua starch. The prepared starch may be applied in developing various formulations of food and pharmaceutical importance.

Background:: The topical drug delivery system has gained more attention in recent years as compared to oral and parenteral drug delivery. However, owing to the barrier function of the skin’s topmost layer, only a few drug molecules can be administered by this route. Therefore, encapsulating the drugs in glycerosomes is one potential solution to this problem. Glycerosomes are vesicular drug delivery systems primarily made up of large concentrations of glycerol, phospholipid, water, and other active ingredients. Objective:: The main aim of this review is to summarize the most recent information on the encapsulated vesicular system used in cosmetic preparations, specifically glycerosomes made from both synthetic and naturally occurring plant bioactive substances. Purpose:: Glycerosomes offer many benefits, including increased efficacy, better stability, improve absorption, drug targeting at specific sites, and delivering the same at a predetermined rate. Method:: The mechanism behind the penetration of glycerosomes is the hydration and lipid fluidization of skin, fabricated by glycerol. Result:: Numerous methods have been reported for the formulation of glycerosomes, including the thin film hydration method, reverse-phase evaporation, solvent spherule, detergent removal method, and so on. Conclusion:: Researchers are currently investigating the potential of glycerosomes as nanocarriers for natural bioactive and synthetic drugs. This review describes the structure of glycerosomes, preparation techniques, applications, distinctions from liposomes, and benefits of glycerosomes.

Male Wistar rats were divided into 6 groups (A-F) and treated as --Group A: Control; Group B: Nerium indicum leaves extract (NLE; 25 mg/kg b wt); Group C: Nerium indicum leaves extract (NLE; 25 mg /kg b wt) + selenium extract (Se; 0.5 mg/ kg b wt); Group D: Nerium indicum leaves extract (NLE; 25 mg/ kg b wt) + Curcuma longa rhizome extract (CRE; 200 mg/kg b wt); Group E: Selenium extract (Se; 0.5 mg/ kg b wt); Group F: Curcuma longa rhizome extract (CRE; 200 mg/kg b wt).Serum calcium and phosphate levels were analyzed on 15 and 30 days after exposure of above mentioned treatments.Rats from group B showed a progressive decrease in serum calcium level as compared to group A (control) from day 15 to day 30.In group C and group D the serum calcium levels showed a decrease on day 15 as compared to the control (group A).On day 30, the levels in group C and group D were increased as compared to group B but it is still hypocalcemic as compared to control.This shows that the serum calcium levels were slightly recovered as compared to group B after administration of selenium and Curcuma longa rhizome extract after 30 days.There is no alteration in serum calcium levels of group E and F as compared to group A.Exposure of Nerium indicum leaves extract (group B) to rats showed a decrease in serum phosphate level at days 15 and 30 as compared to control (group A).There is increase in serum phosphate levels of group C and group D on day 15 and 30 as compared to group B. This clearly indicated that the phosphate levels which were decreased by exposure to Nerium indicum leaves extract recovered after administration of selenium and Curcuma longa rhizome extract.No alteration was noticed in serum phosphate levels of group E and group F.

The developments of pH–sensitive liposomes which are stable at physiological pH i.e. (6.8–7.4) have not explored much up until now. These lipid vesicles will go through destabilization and attain fusogenic properties in acidic conditions leading to liberation of aqueous contents. Carboplatin, included in the family of alkylating agent was found to exhibit adverse effects like myelo suppression, ion thrombocytopenia and leucopenia. Therefore, in order to circumvent these effects, carboplatin pH-sensitive liposomes for specific delivery is the ideal criteria and it poses a great challenge since the water-soluble drugs exhibited very low entrapment efficiency. The essential portion of study was evaluated using the Design Expert software 8. The pH-sensitive liposomes were optimized using Central composite design and one factor Response surface model design method and were prepared by film hydration method. Two formulation variables like drug: lipid ratio (X1) and volume of hydration media (X2) used to vary at three different levels and the other three variables viz. temperature, speed of rotation and vacuum applied were kept constant. The Response surface and contour plots were figured to elicit the effects of interaction of variables on the overall entrapment efficiency. pH-sensitive liposomes of carboplatin have been regarded as a promising delivery systematic approach in order to target tumor tissue as evaluated by the pre-clinical studies in both in vitro and ex-vivo conditions.