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Mycoplasmas are opportunistic parasites and some species are suggested to preferentially colonize tumor tissue in cancer patients. We could demonstrate that the annotated thymidine phosphorylase (TP) gene in the genome of Mycoplasma hyorhinis encodes a pyrimidine nucleoside phosphorylase (PyNPHyor) that not only efficiently catalyzes thymidine but also uridine phosphorolysis. The kinetic characteristics of PyNPHyor-catalyzed nucleoside and nucleoside analogue (NA) phosphorolysis were determined. We demonstrated that the expression of such an enzyme in mycoplasma-infected cell cultures dramatically alters the activity of various anticancer/antiviral NAs such as 5-halogenated pyrimidine nucleosides, including 5-trifluorothymidine (TFT). Due to their close association with human cancers, the presence of mycoplasmas may markedly influence the therapeutic efficiency of nucleoside-based drugs. [ABSTRACT FROM AUTHOR]

Potential anticancer therapy with the fumagillin analog TNP-470 was investigated in the present project using subcutaneously growing rhabdomyosarcomas in rats. Specifically, influences of different tumor sizes at the start of treatment as well as dose/schedules were evaluated with this angiogenesis inhibitor. The results show a significant (p = < or = 0.01) reduction of the growth rate, even for relatively large-sized (> 7 cm3) tumors, when 50 mg/kg TNP-470 was used every other day for up to 3 or 5 injections. With 30 mg/kg TNP-470 injections, effects were seen only with tumors measuring < 7 cm3. The histologic examinations demonstrate an increase in necrosis, both in the center and in the peripheral part of TNP-470-treated tumors. Overall, both tumor volume and drug dose determine treatment outcome with the rat rhabdomyosarcoma. The results suggest that angiogenesis inhibitors could represent a valid component in the treatment of progressive tumor growth, also of large tumors as often encountered in clinics. The antivasculature therapy might also improve hypoxia/necrosis-related therapeutic approaches. [ABSTRACT FROM AUTHOR]

Skin diseases often give multifactorial damages; therefore, the development of multifunctional compounds represents a suitable approach especially against disorders that are induced by oxidative stress. Thus, taking into account the successful results we achieved on benzimidazoles, we have devised a new series of isosteric benzothiazoles and investigated their antioxidant, photoprotective, antifungal and antiproliferative activity. Particular attention has been paid to synergistic antioxidant and photoprotective properties. For compounds 9a and 10a , a multifunctional profile was outlined, supported by an excellent filtering capacity, mainly UVB, which has higher capacities than those of the reference PBSA which is currently in the market as a UV sunscreen filter. The two compounds were also the best in terms of growth inhibition of dermatophytes and Candida albicans, and 10a also showed good antioxidant activity. Furthermore, 9a was also effective on melanoma tumor cells (SK-Mel 5), making these compounds good candidates in the development of new skin protective and preventive agents.

In this work, a series of novel 1,2,3-triazolyl-coumarin hybrid systems were designed as potential antitumour agents. The structural modification of the coumarin ring was carried out by Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition of 7-azido-4-methylcoumarin and terminal aromatic alkynes to obtain 1,4-disubstituted 1,2,3-triazolyl-coumarin conjugates 2a - g , bis(1,2,3-triazolyl-coumarin)benzenes 2h - i and coumarin-1,2,3-triazolyl-benzazole hybrids 4a - b . The newly synthesised hybrid molecules were investigated for in vitro antitumour activity against five human cancer cell lines, colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma H 460, human T-lymphocyte cells CEM, cervix carcinoma cells HeLa, as well as human dermal microvascular endothelial cells (HMEC-1). Most of these compounds showed moderate to pronounced cytotoxic activity, especially towards MCF-7 cell lines with IC 50 = 0.3-32 μM. In addition, compounds 2a - i and 4a - b were studied by UV-Vis absorption and fluorescence spectroscopy and their basic photophysical parameters were determined.

Aim: The aim of this study was to synthesize new coumarin-based compounds and evaluate their antibacterial and antitumor potential. Results: Using transition metal-catalyzed reactions, a series of 7-hydroxycoumarin derivatives were synthesized with aliphatic and aryl moiety attached directly at C-3 of the coumarin ring and through the ethynyl or 1,2,3-triazole linker. The 3-substituted coumarin derivative bearing bistrifluoromethylphenyl at the C-4 position of 1,2,3-triazole ( 33 ) showed strong and selective antiproliferative activity against cervical carcinoma cells. The 7-hydroxy-4-methylcoumarin with a phenyl ring directly attached to coumarin at C-3 ( 10 ) showed good potency against the methicillin-resistant  Staphylococcus aureus and vancomycin-resistant strains. Conclusion: The most active coumarin derivatives owe their antiproliferative potential to the 3,5-ditrifluoromethylphenyl substituent (in 33 ) and antibacterial activity to the aromatic moiety (in 10 ); their structure can be optimized further for improved effect.

Background: Community pharmacists acknowledge to have an important role in providing pharmaceutical care during preconception, pregnancy and lactation. However, pharmacists' knowledge and counseling regarding this topic is still insufficient. Hence, educational initiatives are urgently needed., Objectives: To assess the impact of a blended learning program ('intervention') on community pharmacists' barriers, knowledge, and counseling practice with regard to preconception, pregnancy and lactation., Methods: A pre-post study was performed in collaboration with 40 randomly selected pharmacies belonging to a large pharmacy chain in Belgium. All pharmacists employed in these pharmacies were eligible to participate in a blended learning program consisting of an e-learning and an on-site training day. Data were collected using online surveys, mystery shopping visits and pharmacy records. Pharmacy conversations were assessed on information gathering, dispensed product, and case-specific information. A retention knowledge test was completed 3-6 months after the intervention., Results: In total, 60 pharmacists completed the post-intervention surveys (response rate: 95%). The total number of barriers decreased after the intervention, while organizational barriers such as lack of privacy (73%) and lack of time (67%) became more prevalent. Pharmacists' short and long-term knowledge improved after the intervention (p ≤ 0.001), although knowledge declined again over time (p ≤ 0.001). During counseling, pharmacists more often spontaneously provided information about folic acid when dispensing a pregnancy test, and more often suggested the correct dose/dosage for the dispensed OTC-product against pregnancy-related nausea. However, poor information gathering, dosing errors and incomplete information were still observed., Conclusion: The blended learning decreased pharmacists' barriers and improved their short- and long-term knowledge, while counseling practice only partially improved. Hence, the blended learning was insufficient to enhance pharmacists' information gathering competences and to fully implement pharmaceutical care services with regard to preconception, pregnancy and lactation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In the last years, many efforts have been made to find colchicine derivatives with reduced toxicity. Additionally, the deregulation of amino acid uptake by cancer cells provides an opportunity to improve anticancer drug effectiveness., Objective: To design new colchicine derivatives with reduced cytotoxicity and enhanced selectivity by means of introducing aminoacyl groups., Methods: 34 colchicine analogues bearing L- and D-amino acid pendants were synthetized and characterized by NMR, IR and MS techniques. Cytotoxicity and antimitotic properties were assessed by spectrophotometry and cell cycle assays. Oncogene downregulation was studied by RTqPCR whereas in vivo studies were performed in SCID mice., Results: Compounds exhibit high antiproliferative activities at the nanomolar level while being, in general, less cytotoxic than colchicine. Most compounds inhibit the polymerization of tubulin in a way similar to colchicine itself, with L-amino acid derivatives being the most active in the inhibition of tubulin polymerization. All selected compounds caused cell cycle arrest at the G2/M phase when tested at 1 μM. More specifically, Boc-L-proline derivative 6 arrested half of the population and showed one of the highest Selectivity Indexes. Derivatives 1 (Boc-glycine), 27 (D-leucine) and 31 (Boc-glycine-glycine) proved fairly active in downregulating the expression of the c-Myc, hTERT and VEGF oncogenes, with compound 6 (Boc-L-proline) having the highest activity. This compound was shown to exert a potent anti-tumor effect when administered intraperitoneally (LD50 > 100 mg/kg for 6, compared with 2.5 mg/kg for colchicine)., Conclusion: Compound 6 offers an opportunity to be used in cancer therapy with less toxicity problems than colchicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Benzazole and coumarin derivatives are one of the most privileged heterocyclic substructures in the medicinal chemistry with well-known biological features, which include a wide range of versatile biological activities as well as excellent spectroscopic characteristics thus offering their potential application in many research fields., Objective: The prepared iminocoumarins were synthesized to evaluate their antioxidative potential by using ABTS and FRAP assays and in vitro antiproliferative activity., Methods: A series of coumarin derivatives containing a 2-benzazole motif were synthesized and evaluated for their antioxidative capacity and antiproliferative activity. Their molecular structure incorporates a push-pull functionality: an electron donor donating group at the 7-position with an electron-withdrawing group, such as benzimidazole, benzothiazole and imidazopyridine fragment at the 3-position., Results: The iminocoumarins bearing different substituents on 7-position were evaluated for their antiproliferative activity on tree cancer cells with only 4 compounds showing the antiproliferative activity. The most active derivative was N,N-diethylamino substituted benzimidazole derivative 4d and imidazo[4,5-b]pyridine analogue 6b, both also displayed selective activity toward CEM with submicromolar inhibitory concentration (0.059 μM; 0.17 ± 0.09, respectively). The inhibitory effect of 4d and 6b derivatives on the cell-cycle progression of HeLa cells was studied. A flow cytometric analysis of the HeLa cells indicated an appreciable cell-cycle arrest in a dose-dependent manner. Antioxidant properties were studied by ABTS and FRAP assays and obtained results revealed that the most promising antioxidant has proven to be compound 3b while other compounds, in general, showed moderate to very low antioxidative capacity in both assays., Conclusion: Unsubstituted benzimidazole derivatives bearing hydroxyl group on iminocoumarin nuclei exhibited the most prominent antioxidant potential in ABTS assay (3b; 40.5 ± 0.01). The most significant and selective antiproliferative activity was displayed by compounds 4d and 6b (0.059 μM; 0.17 ± 0.09, respectively), which were chosen as lead compounds for further optimization and rational design to obtain more active and selective antiproliferative agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In the search for scaffolds for multifunctional compounds we investigated the structure activity relationship of a class of benzimidazole derivatives bearing 5-membered ring. The newly synthesized and the already known compounds were divided into three classes that present different substituent at 5 position of the benzimidazole ring (-H, -COOH or -SO 3 H) and different heterocycle at position 2 (thiophene, furan or pyrrole). All the derivatives were synthesized and tested to determine their photoprotective profile against UV rays, in vitro antioxidant capacity against different radicals (DPPH and FRAP test), antifungal inhibitory activity (dermatophytes and Candida albicans ), antiviral and antiproliferative activity. A Structure-Activity Relationship study indicated compound 10 , bearing a pyrrole heterocycle on the benzimidazole ring, as the best multifunctional derivative of the series and as potential candidate for the development of drugs especially in case of melanoma.

Background: Although preferably avoided, pregnant and lactating women often use medicines, including potentially inappropriate products. Pregnant women also commonly search for online information on medication. This underscores the need for appropriate counseling by healthcare professionals, including community pharmacists. However, little is known about pharmacists' perceptions and barriers towards this role, nor about their knowledge and counseling practice., Objectives: To explore licensed pharmacists' attitudes, barriers, knowledge and counseling practice regarding pharmaceutical care during preconception, pregnancy and lactation., Methods: All pharmacists employed in 40 randomly selected pharmacies of a Belgian pharmacy chain ('Surplus Network') were asked to complete an online survey between September 2018-February 2019. The survey assessed pharmacists' attitudes and current practice regarding their role, as well as barriers and knowledge. Additionally, the 40 pharmacies were visited twice in December 2017 by simulated patients. The scenarios included a request for a pregnancy test and for an over-the-counter (OTC) product to treat pregnancy-related nausea., Results: All 63 invited pharmacists completed the survey. For all attitude-related statements, at least 80% agreed that pharmacists should take up the presented roles. However, for only 1 in 5 statements did at least 80% report currently taking up these roles for all or most patients. Most commonly reported barriers related to difficulties identifying the woman's status (71%) and lack of education (67%). The median score for the knowledge test was 23/45 (range: 6-36). The mystery shopping showed inadequate questioning and insufficient counseling. Only in 10% of cases was folic acid intake spontaneously discussed; in 39% of cases, incorrect advice about the dispensed OTC-product was given., Conclusion: Pharmacists acknowledged having an important role during preconception, pregnancy and lactation, but currently do not provide pharmaceutical care in this area to most patients. Educational programs are urgently needed to improve licensed pharmacists' knowledge and counseling regarding this topic., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Oxidative stress is the product or aetiology of various multifactorial diseases; on the other hand, the development of multifunctional compounds is a recognized strategy for the control of complex diseases. To this end, a series of benzothiazole derivatives was synthesized and evaluated for their multifunctional effectiveness as antioxidant, sunscreen (filter), antifungal and antiproliferative agents. Compounds were easily synthesized via condensation reaction between 2-aminothiophenols and different benzaldehydes. SAR study, particularly in position 2 and 6 of benzothiazoles, led to the identification of 4g and 4k as very interesting potential compounds for the design of multifunctional drugs. In particular, compound 4g is the best blocker of hERG potassium channels expressed in HEK 293 cells exhibiting 60.32% inhibition with IC 50  = 4.79 μM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)