Publications by authors named "Silvia Cesarini"

8 Publications

  • Page 1 of 1

Stereoselective Access to Antimelanoma Agents by Hybridization and Dimerization of Dihydroartemisinin and Artesunic acid.

ChemMedChem 2021 Jul 7;16(14):2270-2277. Epub 2021 May 7.

Department of Biological and Ecological Sciences, Univeristy of Viterbo, Via S.C. De Lellis s.n.c., 01100, Viterbo, Italy.

A library of five hybrids and six dimers of dihydroartemisinin and artesunic acid has been synthetized in a stereo-controlled manner and evaluated for the anticancer activity against metastatic melanoma cell line (RPMI7951). Among novel derivatives, three artesunic acid dimers showed antimelanoma activity and cancer selectivity, being not toxic on normal human fibroblast (C3PV) cell line. Among the three dimers, the one bearing 4-hydroxybenzyl alcohol as a spacer showed no cytotoxic effect (CC >300 μM) and high antimelanoma activity (IC =0.05 μM), which was two orders of magnitude higher than that of parent artesunic acid, and of the same order of commercial drug paclitaxel. In addition, this dimer showed cancer-type selectivity towards melanoma compared to prostate (PC3) and breast (MDA-MB-231) tumors. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses. Qualitative structure activity relationships highlighted the role of artesunic acid scaffold in the control of toxicity and antimelanoma activity.
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http://dx.doi.org/10.1002/cmdc.202100196DOI Listing
July 2021

Artemisinin Derivatives with Antimelanoma Activity Show Inhibitory Effect against Human DNA Topoisomerase 1.

ACS Med Chem Lett 2020 May 10;11(5):1035-1040. Epub 2020 Apr 10.

Dipartimento di Biologia, Università di Padova Distaccato presso il "Centro Linceo Beniamino Segre" Accademia Nazionale dei Lincei, Palazzo Corsini, Via della Lungara 10, 00165 Rome, Italy.

Artesunic acid and artemisinin are natural substances with promiscuous anticancer activity against different types of cancer cell lines. The mechanism of action of these compounds is associated with the formation of reactive radical species by cleavage of the sesquiterpene pharmacophore endoperoxide bridge. Here we suggested topoisomerase 1 as a possible molecular target for the improvement of the anticancer activity of these compounds. In this context, we report that novel hybrid and dimer derivatives of artesunic acid and artemisinin, bearing camptothecin and SN38 as side-chain biological effectors, can inhibit growth of yeast cells overexpressing human topoisomerase 1 and its enzymatic activity . These derivatives showed also anticancer activity in melanoma cell lines higher than camptothecin and paclitaxel. molecular docking calculations highlighted a common binding mode for the novel derivatives, with the sesquiterpene lactone scaffold being located near the traditional recognition site for camptothecin, while the bioactive side-chain effector laid in the camptothecin cleft.
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http://dx.doi.org/10.1021/acsmedchemlett.0c00131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236541PMC
May 2020

Alternative Oils Tested as Feedstocks for Enzymatic FAMEs Synthesis: Toward a More Sustainable Process.

Biotechnol Prog 2017 Sep 18;33(5):1209-1217. Epub 2017 Sep 18.

Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, Spain.

Previously isolated and characterized Pseudomonas lipases were immobilized in a low-cost MP-1000 support by a re-loading procedure that allowed a high activity per weight of support. Immobilized LipA, LipC, and LipCmut lipases, and commercial Novozym® 435 were tested for fatty acid methyl ester (FAMEs) synthesis using conventional and alternative feedstocks. Triolein and degummed soybean oils were used as model substrates, whereas waste cooking oil and M. circinelloides oil were assayed as alternative, low cost feedstocks, whose free fatty acid (FFA), and acylglyceride profile was characterized. The reaction conditions for FAMEs synthesis were initially established using degummed soybean oil, setting up the best water and methanol concentrations for optimum conversion. These conditions were further applied to the alternative feedstocks and the four lipases. The results revealed that Pseudomonas lipases were unable to use the FFAs, displaying a moderate FAMEs synthesis, whereas a 44% FAMEs production was obtained when M. circinelloides oil was used as a substrate in the reaction catalysed by Novozym® 435, used under the conditions established for degummed soybean oil. However, when Novozym® 435 was tested under previously described optimal conditions for this lipase, promising values of 85 and 76% FAMEs synthesis were obtained for waste cooking oil and M. circinelloides oil, respectively, which might result in promising, nonfood, alternative feedstocks for enzymatic biodiesel production. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1209-1217, 2017.
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http://dx.doi.org/10.1002/btpr.2558DOI Listing
September 2017

Saturation mutagenesis in selected amino acids to shift Pseudomonas sp. acidic lipase Lip I.3 substrate specificity and activity.

Chem Commun (Camb) 2015 Jan;51(7):1330-3

Bioscience Department, Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay.

Several Pseudomonas sp. CR611 Lip I.3 mutants with overall increased activity and a shift towards longer chain substrates were constructed. Substitution of residues Y29 and W310 by smaller amino acids provided increased activity on C18-substrates. Residues G152 and S154, modified to study their influence on interfacial activation, displayed a five and eleven fold increased activity.
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http://dx.doi.org/10.1039/c4cc08477bDOI Listing
January 2015

Fast and economic immobilization methods described for non-commercial Pseudomonas lipases.

BMC Biotechnol 2014 Apr 22;14:27. Epub 2014 Apr 22.

Department of Microbiology, University of Barcelona, Av, Diagonal 643, 08028 Barcelona, Spain.

Background: There is an increasing interest to seek new enzyme preparations for the development of new products derived from bioprocesses to obtain alternative bio-based materials. In this context, four non-commercial lipases from Pseudomonas species were prepared, immobilized on different low-cost supports, and examined for potential biotechnological applications.

Results: To reduce costs of eventual scaling-up, the new lipases were obtained directly from crude cell extracts or from growth culture supernatants, and immobilized by simple adsorption on Accurel EP100, Accurel MP1000 and Celite®545. The enzymes evaluated were LipA and LipC from Pseudomonas sp. 42A2, a thermostable mutant of LipC, and LipI.3 from Pseudomonas CR611, which were produced in either homologous or heterologous hosts. Best immobilization results were obtained on Accurel EP100 for LipA and on Accurel MP1000 for LipC and its thermostable variant. Lip I.3, requiring a refolding step, was poorly immobilized on all supports tested (best results for Accurel MP1000). To test the behavior of immobilized lipases, they were assayed in triolein transesterification, where the best results were observed for lipases immobilized on Accurel MP1000.

Conclusions: The suggested protocol does not require protein purification and uses crude enzymes immobilized by a fast adsorption technique on low-cost supports, which makes the method suitable for an eventual scaling up aimed at biotechnological applications. Therefore, a fast, simple and economic method for lipase preparation and immobilization has been set up. The low price of the supports tested and the simplicity of the procedure, skipping the tedious and expensive purification steps, will contribute to cost reduction in biotechnological lipase-catalyzed processes.
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http://dx.doi.org/10.1186/1472-6750-14-27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003287PMC
April 2014

Combining phospholipases and a liquid lipase for one-step biodiesel production using crude oils.

Biotechnol Biofuels 2014 Feb 26;7(1):29. Epub 2014 Feb 26.

Department of Microbiology, University of Barcelona, Avenida Diagonal 643, Barcelona 08028, Spain.

Background: Enzymatic biodiesel is becoming an increasingly popular topic in bioenergy literature because of its potential to overcome the problems posed by chemical processes. However, the high cost of the enzymatic process still remains the main drawback for its industrial application, mostly because of the high price of refined oils. Unfortunately, low cost substrates, such as crude soybean oil, often release a product that hardly accomplishes the final required biodiesel specifications and need an additional pretreatment for gums removal. In order to reduce costs and to make the enzymatic process more efficient, we developed an innovative system for enzymatic biodiesel production involving a combination of a lipase and two phospholipases. This allows performing the enzymatic degumming and transesterification in a single step, using crude soybean oil as feedstock, and converting part of the phospholipids into biodiesel. Since the two processes have never been studied together, an accurate analysis of the different reaction components and conditions was carried out.

Results: Crude soybean oil, used as low cost feedstock, is characterized by a high content of phospholipids (900 ppm of phosphorus). However, after the combined activity of different phospholipases and liquid lipase Callera Trans L, a complete transformation into fatty acid methyl esters (FAMEs >95%) and a good reduction of phosphorus (P <5 ppm) was achieved. The combination of enzymes allowed avoidance of the acid treatment required for gums removal, the consequent caustic neutralization, and the high temperature commonly used in degumming systems, making the overall process more eco-friendly and with higher yield. Once the conditions were established, the process was also tested with different vegetable oils with variable phosphorus contents.

Conclusions: Use of liquid lipase Callera Trans L in biodiesel production can provide numerous and sustainable benefits. Besides reducing the costs derived from enzyme immobilization, the lipase can be used in combination with other enzymes such as phospholipases for gums removal, thus allowing the use of much cheaper, non-refined oils. The possibility to perform degumming and transesterification in a single tank involves a great efficiency increase in the new era of enzymatic biodiesel production at industrial scale.
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http://dx.doi.org/10.1186/1754-6834-7-29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015511PMC
February 2014

Lipase improvement: goals and strategies.

Comput Struct Biotechnol J 2012 15;2:e201209005. Epub 2012 Oct 15.

Department of Microbiology, University of Barcelona. Av. Diagonal 643, 08028-Barcelona. Spain.

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http://dx.doi.org/10.5936/csbj.201209005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962121PMC
June 2014

Genetic relationships among Italian and Mexican maize-rhizosphere Burkholderia cepacia complex (BCC) populations belonging to Burkholderia cenocepacia IIIB and BCC6 group.

BMC Microbiol 2011 Oct 13;11:228. Epub 2011 Oct 13.

ENEA (Italian National Agency for New Technologies, Energy and Sustainable Development) Casaccia Research Center-Technical Unit for Sustainable Development and Innovation of Agro-Industrial System, Via Anguillarese 301, 00123 S, Maria di Galeria, Rome, Italy.

Background: A close association between maize roots and Burkholderia cepacia complex (BCC) bacteria has been observed in different locations globally. In this study we investigated by MultiLocus Restriction Typing (MLRT) the genetic diversity and relationships among Burkholderia cenocepacia IIIB and BCC6 populations associated with roots of maize plants cultivated in geographically distant countries (Italy and Mexico), in order to provide new insights into their population structure, evolution and ecology.

Results: The 31 B. cenocepacia IIIB and 65 BCC6 isolates gave rise to 29 and 39 different restriction types (RTs), respectively. Two pairs of isolates of B. cenocepacia IIIB and BCC6, recovered from both Italian and Mexican maize rhizospheres, were found to share the same RT. The eBURST (Based Upon Related Sequence Types) analysis of MLRT data grouped all the B. cenocepacia IIIB isolates into four clonal complexes, with the RT-4-complex including the 42% of them, while the majority of the BCC6 isolates (94%) were grouped into the RT-104-complex. These two main clonal complexes included RTs shared by both Italian and Mexican maize rhizospheres and a clear relationship between grouping and maize variety was also found. Grouping established by eBURST correlated well with the assessment using unweighted-pair group method with arithmetic mean (UPGMA). The standardized index of association values obtained in both B. cenocepacia IIIB and BCC6 suggests an epidemic population structure in which occasional clones emerge and spread.

Conclusions: Taken together our data demonstrate a wide dispersal of certain B. cenocepacia IIIB and BCC6 isolates in Mexican and Italian maize rhizospheres. Despite the clear relationship found between the geographic origin of isolates and grouping, identical RTs and closely related isolates were observed in geographically distant regions. Ecological factors and selective pressure may preferably promote some genotypes within each local microbial population, favouring the spread of a single clone above the rest of the recombinant population.
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http://dx.doi.org/10.1186/1471-2180-11-228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377929PMC
October 2011