Drug interaction has turned into the preeminent regarding issues for a prescriber during polypharmacy. The foremost objective of this research was to form a complex between linagliptin and rabeprazole sodium by in vitro interactions. The interactions between the drugs have been examined by monitoring some chromatographic and spectroscopic analyses viz. TLC, HPLC, FT-IR, UV, Job’s plot, conductometric titrations, and Ardon’s spectrophotometric strategy. Rabeprazole sodium formed a stable complex with linagliptin, which was ensured from the insight of these analytical data. The developed complex’s bright spot was clearly watched in the TLC plate. The retention time (Rt) of the formed complex was 5.303 min, where the Rt were 3.364 and 3.103 min for linagliptin and rabeprazole sodium, respectively, in HPLC chromatograms. In FT-IR and UV spectra of the formed complex revealed some disappearance of characteristic peaks that affirmed the complexation. All of the variations of the spectrophotometric and chromatographic properties from the antecedent drugs indicated the drug-drug interaction. Another crucial fact for the experimental aim was to affirm the assumed drug interaction by in vivo model examination. The assessment of anti-diabetic property on alloxan-induced Swiss albino mice proved significant in vivo interaction between the drugs. It was outlined from the animal study that the hypoglycemic activity of linagliptin might be significantly affected due to the complex formation of the drug with a proton pump inhibitor (PPI). Nonetheless, it is the primary outcome of the interaction, which recommends the bigger in vivo study or clinical monitoring on the human model.

Bioassay-guided extraction and fractionation of the aqueous methanolic extract of the cones of Pinus densiflora (Pinaceae) afforded one new labdane-type diterpene aldehyde, 15-nor-14-oxolabda-8(17),12 E-diene-18-oic acid, along with eight known diterpenes. Their structures were elucidated using spectroscopic methods as well as by comparison with previously reported data. The isolates showed antibacterial (Propionibacterium acnes) and antifungal activities.

Quinone type compound, pulsaquinone 1, isolated from the aqueous ethanol extract of the roots of Pulsatilla koreana exhibited antimicrobial activities against an anaerobic non-spore-forming gram-positive bacillus, Propionibacterium acnes, which is related with the pathogenesis of the inflamed lesions in a common skin disease, acne vulgaris. Compound 1 was unstable on standing and thus converted to more stable compound 2, namely hydropulsaquinone by hydrogenation, whose activity was comparable to mother compound 1 (MIC for 1 and 2 against P. acnes: 2.0 and 4.0 microg/mL, respectively). Other structurally-related quinone derivatives (3-13) were also tested for structure-activity relationship against anaerobic and aerobic bacteria, and fungi. The antimicrobial activity was fairly good when the quinone moiety was fused with a nonpolar 6- or 7-membered ring on the right side whether or not conjugated (1,4-naphtoquinone derivatives 3-5), while simple quinone compounds 6-9 showed poor activity. It seems that the methoxy groups at the left side of the quinone function deliver no considerable antimicrobial effect.

The foremost aim of this thermodynamic study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) profiles of linagliptin (LG), rabeprazole sodium (RS), and their 1:1 formed complex by interacting with bovine serum albumin (BSA) at physiological pH 7.4. The molecular interactions of these ligands with the desired biomolecule were substantiated by the spectral quelling of fluorescence intensity of BSA. The fluorescent test and molecular docking revealed that the quenching mechanism was a spontaneous and exothermic static process, and the protein gained its secondary structure due to the interactions. The spectroscopic method was exercised to determine the thermodynamic factors that supported the interactions mediated by van der Waals forces and hydrogen bonds. The activation energy of the formed complex was higher than its precursor drugs while interacting with BSA, and the energy transformation profiles were studied by UV-fluorescence overlaid curves according to Förster resonance energy transfer (FRET) theory. The double log plot verified that these ligands bound with protein at a 1:1 ratio, which was confirmed by the approximately estimated values of the binding parameters. The drastically lower value of the binding constant of the formed complex suggested the lower half-life as well as its triggered elimination rate from the cardiovascular system, which may be an initial indicator of the reduced hypoglycemic property of linagliptin. Moreover, the UV-vis and synchronous fluorescence spectroscopic methods affirmed the conformational changes of the BSA due to drug-protein complexation and polarity alterations in the microenvironment of disparate chromophores of the biomolecule.

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