Current Pharmaceutical Biotechnology - Volume 23, Issue 9, 2022

Background: Pinus belongs to the family Pinaceae, represented by several species across the globe. Various parts of the plant including needles are rich in biologically active compounds, such as thunbergol, 3-carene, cembrene, α-pinene, quercetin, xanthone. Of all the alkaloids, the piperidine group is one of the important component and holds considerable medicinal importance. Methods: The group of alkaloids was initially identified from the genus Piper through which a large variety of piperidine molecules have been extracted. The planar structure of this heterocyclic nucleus enables acetamide groups to be added at various ring configurations. Results: Piperidines have gained considerable importance. The broad range of its therapeutic application has paved a way for researchers to implant the nucleus from time to time in diversified pharmacophores and establish new profile. Discussion: Biological functions of piperidine metabolites have been mostly examined on a limited scale, and that most of the findings are preliminary. We have tried to present various clinical applications of piperidine alkaloids in this study that researchers have already attempted to demystify with time. Conclusion: We have also illustrated different types of piperidine structures and their sources in different members of the family Pinaceae with special emphasis on Pinus. Given the importance of the piperidine nucleus, the study will enable the researchers to produce scaffolds of highest therapeutic efficacy.

Ovarian cancer is a lethal type of cancer which is initiated to the ovaries and affects 1 out of every 75 women. Due to the high number of deaths (almost 152,000) related to this cancer, it seems that novel efficient therapeutic methods are required in this field. Beta-glucans are a type of glucose linear polymers which have been proven to have a lot of advantageous activities. Recently, investigations have declared that these polysaccharides have the potential to be used as anti-cancer drugs. These agents are able to affect several mechanisms such as inflammation and apoptosis, and that is how cancers are prone to be affected by them. In this review, we attempt to investigate the role of beta-glucans on ovarian cancer. We hope that this paper would give some novel insights into the field of ovarian cancer treatment.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

Background: Mounting evidence has shown that Cyclin E1 (CCNE1) facilitates various carcinoma progression, but its function in lung adenocarcinoma (LUAD) remains unclear. Objective: Our study aims to explore the significance of CCNE1 in clinical progression and study its biological functions in LUAD. Methods: CCNE1 expressions in LUAD specimens and cells were detected through quantitative realtime polymerase chain reaction (qRT-RCR) and western blot. An immunohistochemistry technique was used to detect CCNE1 expression to explore its association with clinical parameters. The LUAD cells with stable knockdown of CCNE1 were constructed by small interfering RNA. The effect of CCNE1 on LUAD cells proliferation and apoptosis was evaluated through Cell Counting Kit-8 (CCK-8), colony formation, and Annexin V/propidium iodide (AV-PI) assays, respectively. The cell migration and invasion were evaluated by Wound-healing and Transwell assays, respectively. The xenograft and lung metastasis mouse models were introduced to analyze how CCNE1 knockdown affects tumor growth and tumor metastasis. Results: CCNE1 expression was upregulated in LUAD tissue and cells. CCNE1 knockdown inhibited LUAD cellular malignant behavior in vitro and reduced tumor growth and metastasis in vivo. High expression of CCNE1 was correlated with big tumor size, cancer stage, lymph node metastasis, and poor prognosis. Conclusion: CCNE1 overexpression promotes LUAD growth, metastasis, and forebode poor prognosis: it can serve as a new prognostic marker of LUAD.

Background: Quinazolines are a common class of nitrogen-containing heterocyclic scaffolds, which exhibit a broad spectrum of pharmacological activities. Objectives: In the present study, quinazoline and quinazolin-4-one derivatives were prepared, characterized, and evaluated for their biological activity, which may pave the way for possible therapeutic applications. Materials and Methods: New derivatives of quinazoline and quinazolin-4-one were prepared and tested for antiulcerogenic, anti-inflammatory and hepatoprotective activities. Results: The synthesized compounds were characterized by elemental analysis and spectral data. Also, the median lethal doses (LD50s) of compounds 1-3 in rats were 1125, 835 and 1785 mg/kg b.w., respectively. IC50 values of compounds (1-3) as measured by ABTS•+ radical method were 0.8, 0.92 and 0.08 mg/mL, respectively. Antiulcerogenic activity at dose 1/20 LD50 in albino rats was observed at 47.94, 24.60 and 56.45%, respectively. Anti-inflammatory effect at dose 1/20 LD50 of compounds (1-3) was observed in the induced edema model after 120 min. The prepared compounds were found to possess hepato gastric mucosa protective activity against ibuprofen-induced ulceration and LPS-induced liver toxicity, respectively, in rats etc. normalization of oxidative stress biomarkers, and inflammatory mediators were inhibited in peritoneal macrophage cells at a concentration of 100 μg/L. Molecular docking suggested that the most active compounds 1 and 2 could be positioned within the active sites of COX-2 at Arg121 and Tyr356, similarly to ibuprofen (Arg-120, Glu-524, and Tyr-355). The compound 3–COX-2 complex generated by docking revealed intricate interactions with a COX-2 channel. Conclusion: These findings suggest that compounds 1-3 exhibited good antioxidant, antiulcer, and anti-inflammatory activities, and were safe on liver enzymes in rats.

Background: A simple and powerful microextraction procedure, the solvent bar microextraction (SBME), was used for the simultaneous determination of two diuretics, furosemide and spironolactone in human urine and plasma samples, using high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). Methods: The appropriate amount (2 μL) of 1-octanol as an organic solvent confined within 2.5 cm of a porous hollow fiber micro-tube, sealed at both ends was used for this procedure. The conditions for the SBME were optimized in water and the analytical performance was examined in spiked human urine and plasma samples. Results: The optimized method exhibited good linearity (R²> 0.997) over the studied range of higher than 33 to 10⁴μg L^-1 for furosemide and spironolactone in urine and plasma samples, illustrating a satisfactory precision level with RSD values between 2.1% and 9.1%. Discussion: The values of the limits of detection were found to be in the range of 6.39 to 9.67μg L^-1, and extraction recovery #131; 58.8% for both diuretics in urine and plasma samples. The applicability and effectiveness of the proposed method for the determination of furosemide and spironolactone in patient urine samples were tested. Conclusion: In comparison with reference methods, the attained results demonstrated that SBME combined with HPLC-DAD was proved to be simple, inexpensive, and promising analytical technology for the simultaneous determination of furosemide and spironolactone in urine and plasma samples.

Background: Drug delivery systems based on Human Serum Albumin (HSA) have been widely investigated due to their capability to interact with several molecules together with their nontoxicity, non-immunogenicity and biocompatibility. Sorafenib (SOR) is a kinase inhibitor used as the firstline treatment in hepatic cancer. However, because of its several intrinsic drawbacks (low solubility and bioavailability), there is a growing need for discovering new carriers able to overcome the current limitations. Objectives: To study HSA particles loaded with SOR as a thermal responsive drug delivery system. Methods: A detailed spectroscopy analysis of the HSA and SOR interaction in solution was carried out in order to characterize the temperature dependence of the complex. Based on this study, the synthesis of HSA particles loaded with SOR was optimized. Particles were characterized by Dynamic Light Scattering, Atomic Force Microscopy and by spectrofluorometer. Encapsulation efficiency and in vitro drug release were quantified by RP-HPLC. Results: HSA particles were monodispersed in size (≈ 200 nm); encapsulation efficiency ranged from 25% to 58%. Drug release studies that were performed at 37 °C and 50 °C showed that HS5 particles achieved a drug release of 0.430 μM in 72 hours at 50 °C in PBS buffer, accomplishing a 4.6-fold overall SOR release enhancement following a temperature increase from 37 °C to 50 °C. Conclusion: The system herein presented has the potential to exert a therapeutic action (in the nM range) triggering a sustained temperature-controllable release of relevant drugs.