Physicochemical properties, pharmacokinetic studies, DFT approach, and antioxidant activity of nitro and chloro indolinone derivatives.

The process of developing of new drugs is greatly hampered by their inadequate physicochemical, pharmacokinetic, and intrinsic characteristics. In this regard, the selected chloro indolinone, (Z)-6-chloro-3-(2-chlorobenzylidene)indolin-2-one (C1), and nitro indolinone, (Z)-6-chloro-3-(2-nitrobenzylidene)indolin-2-one (C2), were subjected to SwissADME and density function theory (DFT) analysis. For compounds C1 and C2, the BOILED-Egg pharmacokinetic model predicted intestinal absorption, blood-brain barrier (BBB) penetration, and p-glycoprotein interaction. According to the physicochemical analysis, C1 has exceptional drug-like characteristics suitable for oral absorption. Despite only being substrates for some of the major CYP 450 isoforms, compounds C1 and C2 were anticipated to have strong plasma protein binding and efficient distribution and block these isoforms. The DFT study using the B3LYP/6-311G(d,p) approach with implicit water effects was performed to assess the structural features, electronic properties, and global reactivity parameters (GRP) of C1 and C2. The DFT results provided further support for other studies, implying that C2 is more water-soluble than C1 and that both compounds can form hydrogen bonds and (weak) dispersion interactions with other molecules, such as solvents and biomolecules. Furthermore, the GRP study suggested that C1 should be more stable and less reactive than C2. A concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was shown by both C1 and C2. In brief, this finding has provided a strong foundation to explore further the therapeutic potential of these molecules against a variety of human disorders.

Computational pharmacology and computational chemistry of 4-hydroxyisoleucine: Physicochemical, pharmacokinetic, and DFT-based approaches.

Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADMETLab 2.0 was used to determine its important drug-related properties. 4-Hydroxyisoleucine is compliant with important drug-like physicochemical properties and pharma giants' drug-ability rules like Lipinski's, Pfizer, and GlaxoSmithKline (GSK) rules. Pharmacokinetically, it has been predicted to have satisfactory cell permeability. Blood-brain barrier permeation may add central nervous system (CNS) effects, while a very slight probability of being CYP2C9 substrate exists. None of the well-known toxicities were predicted in silico, being congruent with wet lab results, except for a "very slight risk" for respiratory toxicity predicted. The molecule is non ecotoxic as analyzed with common indicators such as bioconcentration and LC50 for fathead minnow and daphnia magna. The toxicity parameters identified 4-hydroxyisoleucine as non-toxic to androgen receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. However, out of seven parameters, not even a single toxicophore was found. The density functional theory (DFT) study provided support to the findings obtained from drug-like property predictions. Hence, it is a very logical approach to proceed further with a detailed pharmacokinetics and drug development process for 4-hydroxyisoleucine.

Caralluma edulis (Apocynaceae): A Comprehensive Review on its Traditional Uses, Phytochemical Profile and Pharmacological Effects.

Caralluma edulis is a well-known species of the genus Caralluma from Apocynaceae, commonly known as chunga. Caralluma species are mostly succulent perennial herbs, several of which are edible species. The plant has an outstanding therapeutic background in the traditional system of treatment. It has been recommended for the treatment of a number medical disorders such as hypertension, Alzheimer's disease, rheumatism, gastric problems and leprosy. Traditionally the stem was boiled in water and this extract was then used to cure diabetes. The pharmacological effects of C. edulis have also been explored in various in vitro and in vivo experiments. In this regard, the extract of the plant exhibited strong antioxidant, and analgesic activity against inflammation as well as xylene-mediated ear edema as topical effects. The significant anti-hyperlipidemic effect of the plant extract is also reported. However, the extract was found insignificant in the reversal of alloxan-induced diabetes in the rabbit model at test doses. These pharmacological effects are strongly supported by the presence of different bioactive phytochemicals in the plant. These groups of compounds include sterols, terpenoids, flavonoids, and pregnane glycosides. C. edulis is a very potential member of the genus Caralluma with strong traditional history, phytochemistry and phytopharmacology, and needs further exploration for clinically used lead compounds. In this review, we have focused on combining different reported data on the traditional uses of the plant, its phytochemical profile and pharmacological effects in different experimental assay along with subsequent future prospects.

Nephroprotective effect of the hydromethanolic extract and fractions of Viola serpens Wall. Histological and hematological evidence.

The current study was planned to examine the nephroprotective effect of the crude extract and its various fractions of Viola serpense Wall against paracetamol-induced toxicity in rabbits. The serum creatinine levels of all fractions, as well as the crude extract, were found to have a greater effect. The effect on urine urea by the n-hexane, ethyl acetate, n-butanol and aqueous fraction in high doses (300 mg/kg b.wt.) and crude extract and chloroform in low doses (150 mg/kg bwts.) were comparatively more effective and comparable to silymarin. The creatinine clearance of the fractions except for chloroform, aqueous at 300 mg/kg and the hydro-methanolic extracts at both doses were highly significant. The histological structures of kidneys in crude extract and chloroform-treated groups showed more improvement at the lower doses. The fractions n-hexane, ethyl acetate and n-butanolic exhibited an inverse dose relationship in the histology of the kidney. However, the aqueous fraction showed a dose-dependent nephroprotective effect. Finally, the crude extract and fractions significantly improved paracetamol-induced nephrotoxicity in rabbits.

Anxiolytic and antidepressant potential of extracts of Duchesnea Indica in animal models.

THIS study was designed to investigate the anxiolytic and antidepressant activity of Duchesnea Indica. The methanolic extract and n-hexane fraction of plant were tested in albino mice (20-30 g of 6-8 week). Safety profile of each extract was determined at different doses. Anxiolytic effect of plant was determined by Elevated Plus Maze and Light and Dark Model at different doses of methanolic and n-hexane extract. Antidepressant activities were assisted by Tail Suspension and Forced Swim Model at different doses. Result illustrated that D. Indica had a significant (P < 0.05) potential of reducing anxiety and depression. The methanolic extract at 100 mg and 200 mg significantly increased the time spend in light region of light and dark model and more time spent in open arm of Elevated Plus Maze model. n-hexane extract at dose of 5 mg and 10 mg/kg significantly increases the time spend in light region of Light and dark model and more time spend in open arm of Elevated Plus Maze model as compare to Control group. Methanolic extract of D. Indica significantly reduced the time of immobility in Tail Suspension and Force Swim Model at Dose of 100 mg and 200mg/kg. n-hexane extract also exhibit anti-depressant effect by reducing the time of immobility in Force swim and tail suspension Model at 100 mg and 200mg/kg dose as compare to control group. From the above observations, it could be assumed that the plant has marked anxiolytic and antidepressant potential. However further additional studies will be necessary to determine the underlying exact mechanism and clinical uses.

In vivo antinociceptive and anti-inflammatory activities of umbelliferone isolated from Potentilla evestita.

This study was designed to evaluate the antinociceptive and anti-inflammatory activities of a compound, umbelliferone, isolated from the chloroform fraction of Potentilla evestita in animal models. When tested against acetic acid-induced noxious stimulus, it significantly prolonged pain threshold and provided 38.38% and 60.95% reduction in abdominal constriction at 5 and 10 mg/kg i.p., respectively. Post-umbelliferone injection evoked significant dose-dependent reduction in noxious stimulation with 33.65% and 58.89% pain attenuation at 5 and 10 mg/kg i.p., respectively, in the initial phase. In the late phase, it illustrated more dominant effect with 37.65% and 63.79% blockade of painful sensation. Similarly, it exhibited significant anti-inflammatory activity during various assessment times (1-5 h) with 46.28% and 66.13% amelioration after 4th of administration against induced oedema. In conclusion, umbelliferone possessed strong antinociceptive and anti-inflammatory activities by inhibiting both peripheral and centrally acting pain mediators.