Crofton weed derived isomers of ageraphorone as potent antifeedant against Plutella xylostella (L.).

Global agricultural production is significantly hampered by insect pests, and the demand for natural pragmatic pesticides with environmental concern remains unfulfilled. Ageratina adenophora (Spreng.) also known as Crofton weed, is an invasive perennial herbaceous plant that is known to possess multiple bioactive compounds.

Effects of Quinidine or Rifampin Co-administration on the Single-Dose Pharmacokinetics and Safety of Rilzabrutinib (PRN1008) in Healthy Participants.

This open-label, phase 1 study was conducted with healthy adult participants to evaluate the potential drug-drug interaction between rilzabrutinib and quinidine (an inhibitor of P-glycoprotein [P-gp] and CYP2D6) or rifampin (an inducer of CYP3A and P-gp). Plasma concentrations of rilzabrutinib were measured after a single oral dose of rilzabrutinib 400 mg administered on day 1 and again, following a wash-out period, after co-administration of rilzabrutinib and quinidine or rifampin. Specifically, quinidine was given at a dose of 300 mg every 8 hours for 5 days from day 7 to day 11 (N = 16) while rifampin was given as 600 mg once daily for 11 days from day 7 to day 17 (N = 16) with rilzabrutinib given in the morning of day 10 (during quinidine dosing) or day 16 (during rifampin dosing).

Synthesis of aminomethyl linked (+)-usnic acid derivatives the Mannich reaction and evaluation of their biological activities.

(+)-Usnic acid (UA), a natural dibenzofuran derivative, abundantly produced by lichens and possess wide number of biomedical applications including antibacterial, anti-inflammatory, anti-oxidant and anticancer activities. In the present study, as series of usnic acid derivatives () were synthesised using Mannich reaction assessed for their antioxidant, α-glucosidase, and anticancer activities. The antioxidant activity showed that compound displayed potent antioxidant activity by scavenging the activities of DPPH and ABTS.

Chemical profiling and simultaneous quantification of major bioactive constituents from Cocculus hirsutus by UPLC-QqQ-MS.

Cocculus hirsutus is a widely used herb in traditional systems of medicine for the treatment of various diseases. In the present study, five alkaloids (1-5), two flavonoids (6-7), one triterpenoid (8), and three steroids (9-10) were isolated from the roots of Cocculus hirsutus and further crude extract was analyzed by LC-Q-Tof-MS/MS in positive ionization mode leading to the identification of ten metabolites through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and with literature data. In addition, a method was developed and validated for the quantification of four bio-active compounds [Sinococuline (1), Magnoflorine (2), (E)-N-feruloyltyramine (3), and 20-Hydroxyecdysone (10)] using UPLC-QqQ-MS in multiple reaction monitoring (MRM) mode for the first time.

Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa.

Background: Efanesoctocog alfa is a new class of factor (F) VIII replacement therapy designed to provide high sustained factor levels for longer by overcoming the von Willebrand factor half-life ceiling.

Objectives: To assess the pharmacokinetics and safety of standard half-life (octocog alfa) and extended half-life (rurioctocog alfa pegol) FVIIIs and efanesoctocog alfa.

Methods: This phase 1 study (NCT05042440; EudraCT 2021-000228-37) enrolled previously treated adult men with severe hemophilia A.

Design, synthesis and biological evaluation of novel lipophilic 2, 5-disubstituted tetrazole analogues of muramyl dipeptide as NOD2 agonists.

A focused library of six new 2, 5-disubstituted tetrazole (2, 5-DST) analogues of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) as potential immunomodulators were synthesized by the bioisosteric replacement of α-amide of d-isoglutamine with 5-substituted tetrazole (5-ST). Another parameter 'lipophilicity' was also considered to improve the pharmacological properties of MDP through the alkylation of 5-substituted tetrazole during synthesis. In total, six 2, 5-DST analogues of MDP were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response.

A review on hydroxy anthraquinones from bacteria: crosstalk's of structures and biological activities.

Anthraquinones (AQ), unveiling large structural diversity, among polyketides demonstrate a wide range of applications. The hydroxy anthraquinones (HAQ), a group of anthraquinone derivatives, are secondary metabolites produced by bacteria and eukaryotes. Plant-based HAQ are well-studied unlike bacterial HAQ and applied as herbal medicine for centuries.

Efanesoctocog alfa for hemophilia A: results from a phase 1 repeat-dose study.

Efanesoctocog alfa (rFVIIIFc-VWF-XTEN; BIVV001) is a new class of factor VIII (FVIII) replacement that breaks the von Willebrand factor-imposed FVIII half-life ceiling. In a phase 1/2a study, single-dose efanesoctocog alfa was well tolerated, and no safety concerns were identified. We evaluated the safety, tolerability, and pharmacokinetics of repeat-dose efanesoctocog alfa in a phase 1 study in previously treated adults (≥150 exposure days) with severe hemophilia A.

Population Pharmacokinetic Analysis of Recombinant Factor VIII Fc Fusion Protein in Subjects With Severe Hemophilia A: Expanded to Include Pediatric Subjects.

Recombinant factor VIII Fc fusion protein (rFVIIIFc) has been indicated for adults and children with hemophilia A. The objective of this article was to build a population pharmacokinetic (PK) model using adult and pediatric data sets and explore relevant dosing scenarios across all ages. The activity-time profiles of rFVIIIFc from 3 clinical studies (all trials registered at https://www.

BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A.

Background: Factor VIII replacement products have improved the care of patients with hemophilia A, but the short half-life of these products affects the patients' quality of life. The half-life of recombinant factor VIII ranges from 15 to 19 hours because of the von Willebrand factor chaperone effect. BIVV001 (rFVIIIFc-VWF-XTEN) is a novel fusion protein designed to overcome this half-life ceiling and maintain high sustained factor VIII activity levels.

UPLC-MS Guided Isolation of New Antifeedant Limonoids from Fruits of .

UPLC-MS guided isolation of CHCl extract from the fruits of yielded two new mexicanolide-type limonoids trichanolide F () and trichanolide G () along with a known compound carapanolide U (). The structures of the limonoids were characterized by extensive spectroscopic analysis (MS, IR, 2D NMR). These limonoids (-) were evaluated for their antifeedancy against F.

Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors.

The aim of the present study is to design and synthesis of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors. The target compounds 4a-n were synthesized by one-pot multicomponent approach with good yields and were characterized by various spectroscopic techniques and finally by single crystal X-ray diffraction method (4j). All the newly-synthesized derivatives have been screened for their α-glucosidase enzyme inhibition activity and acarbose taken as a standard drug.

Free radical scavenging, α-glucosidase inhibitory and anti-inflammatory constituents from Indian sedges, R.Br and L.

Background: R. Br and L are widely used in ayurvedic preparation for the treatment of diabetes and other diseases. The early literature, so far, does not indicate the presence of any bioactive principle isolated from these plants.

Morphological and Chemoprofile (Liquid Chromatography-mass Spectroscopy and Gas Chromatography-mass Spectroscopy) Comparisons of Cyperus scariosus R. Br and Cyperus rotundus L.

Background: Cyperus scariosus (CS) R.Br and Cyperus rotundus (CR) L. belongs to Cyperaceae family which is well-reputed in the traditional systems of medicine.

Antioxidant, hepatoprotective and cytotoxic effects of icetexanes isolated from stem-bark of Premna tomentosa.

The study investigates the antioxidant, hepatoprotective and antiproliferative effects of novel icetexane diterpenoids (ice 1-4) isolated from hexane extract of stem bark of Premna tomentosa. A549, HT-29, MCF-7, MDA-MB-231, A431 cells were used to assess the antiproliferative activity by MTT assay. Cell death induced by apoptosis was determined by morphological assessment studies using acridine orange/ethidium bromide staining (dual staining), mitochondrial potential measurement by JC-1 staining, and cell cycle analysis by propidium iodide staining method by Muse cell analyser.

Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid Transporters on the Cornea: Possible Antiviral Agents Against Ocular HSV-1 Infections.

The aim of this study was to characterize the affinity and permeability patterns of the amino acid ester prodrugs of acyclovir (ACV), L-alanine-ACV (AACV), L-serine-ACV (SACV), L-serine-succinate-ACV (SSACV) and L-cysteine-ACV (CACV) on rabbit primary corneal epithelial cell culture (rPCEC) and on rabbit cornea. Amino acid prodrugs of acyclovir, AACV, SACV, SSACV and CACV were synthesized in our laboratory. Chemical hydrolysis in aqueous buffer, enzymatic hydrolysis in corneal homogenates and transport across freshly excised rabbit cornea of these prodrugs were studied.

Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: interaction with the transporters on Caco-2 cells.

In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied.

Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.

Purpose: To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits.

Methods: Stability of L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) prodrugs was evaluated in various ocular tissues. Dose-dependent toxicity of these prodrugs was also examined in rabbit primary corneal epithelial cell culture (rPCEC) using 96-well based cell proliferation assay.

In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits.

In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was evaluated using microdialysis in rabbits. A corneal well was placed on the cornea of the anesthetized New Zealand White rabbits with implanted linear probes into the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine-tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse for a period of 2 h, following which the drug solution was aspirated and well removed.

Mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells: evidence for the involvement of sodium-dependent vitamin C transporter 2.

Purpose: To investigate the mechanism of L-ascorbic acid uptake by rabbit corneal epithelial cells and to functionally characterize the specific transporter involved in this translocation process.

Methods: Uptake studies were carried out with SIRC (Statens Seruminstitut Rabbit Cornea) and rPCEC (rabbit Primary corneal epithelial cell culture) in 12-well plates using [14C] Ascorbic acid (AA). Uptake was done in the presence of L-ascorbic acid and D-isoascorbic acid to delineate stereospecificity.

Modulation of P-glycoprotein-mediated efflux by prodrug derivatization: an approach involving peptide transporter-mediated influx across rabbit cornea.

The aim of this study was to investigate the modulation of efflux mechanisms using transporter- targeted prodrug derivatization of a model P-gp substrate, quinidine. The L-valine, L-valine-valine esters of quinidine, val-quinidine (VQ), and val-val-quinidine (VVQ) were synthesized in our laboratory, respectively. [(14)C] erythromycin was chosen to delineate the affinity of quinidine (Q) toward P-gp.

Simultaneous modulation of transport and metabolism of acyclovir prodrugs across rabbit cornea: An approach involving enzyme inhibitors.

The aim of this study is to identify the class of enzymes responsible for the hydrolysis of amino acid and dipeptide prodrugs of acyclovir (ACV) and to modulate transport and metabolism of amino acid and dipeptide prodrugs of acyclovir by enzyme inhibitors across rabbit cornea. l-Valine ester of acyclovir, valacyclovir (VACV) and l-glycine-valine ester of acyclovir, gly-val-acyclovir (GVACV) were used as model compounds. Hydrolysis studies of VACV and GVACV in corneal homogenate were conducted in presence of various enzyme inhibitors.