Research Groups‎ > ‎

Organic Chemistry (CHIM/06)

Head of Laboratory: BOTTA Bruno (Chimica e tecnologie del farmaco)
Sito web: http://botta-lab.asw.bz/
http://dctf.uniroma1.it/dipartimento/persone/docenti/professori-ordinari/botta-bruno

Main research Topics:

1) Isolation, biotransformation, structure elucidation and synthesis of biologically active compounds from medicinal plants;
2) Discovery and development of small organic molecules and/or natural compounds targeting selectively pathways hyperactivated in cancer stem cells (e.g.Hedgehog and Notch signalling pathways);
3) Design and synthesis of positively charged linkers for bioconjugate-drug development with potential application in nanomedicine and diagnostic field;
4) Synthesis of fluorescent probes selective on tauprotein for early diagnosis of Alzheimer’s disease;
5) Synthesis of artificial receptors endowed with suitable chemical and physical properties which make them applicable in molecular recognition and drug delivery;
6) Synthesisof resorc[4]arene-based system asnew artificial linkers in site directedimmobilization of antibodies for immunosensors and biosensorsdevelopment.

National and International Collaboration:

Al-Jamal K. (King’s College London); Ascenzioni F. (Sapienza University, Department of Biology and Biotechnology, Italy); Boffi A. (Sapienza University, Department of Biochemistry, Italy); Mazzei F. (Sapienza University, Department of Chemistry and Technology of Drugs, Italy); Caliceti P. (University of Padova, Department of Pharmaceutical and Pharmacological Sciences, Italy); Damia G. (Mario Negri Institute for Pharmacological Research, Italy); Di Marcotullio L. (Sapienza University, Department of Molecular Medicine, Italy); Glisic S. (Institute of Nuclear Sciences, Serbia); Limatola C. (Sapienza University, Department of Physiology and Pharmacoloy, Italy); Mancia F. (Columbia University, Department of Physiology and Cellular Biophysics, USA); Mannina L. (Sapienza University, Department of Chemistry and Technology of Drugs, Italy); Schneider G. (Karolinska Institutet, Sweden); Screpanti I. (Sapienza University, Department of Molecular Medicine, Italy); Terenzi H. (Universidade Federal de Santa Catarin, Brasil); Turano P. (CERM University of Florence, Italy); Ulukaya E. (Medical School of Uludag University, Turkey).

Facilities:

UHPLC Thermoscientific Dionex Ultimate 3000 series
Bruker Av-400 400 MHz spectrometer

Settori ERC del gruppo:

PE5_16 - Supramolecular chemistry
PE5_17 - Organic chemistry 

Grants:

Cost Action 160.000 €

Laboratory Members:

Ghirga Francesca (PhD Student)
Ingallina Cinzia (PhD Student)
De Paolis Elisa (PhD Student)
Corradi Silvia (PhD Student)
Balducci Silvia (PhD Student)
Mangiardi Laura (PhD Student)


Pubblication 2015-2018

1. Sobolev, A.P., Mannina, L., Capitani, D., Sanzò, G., Ingallina, C., Botta, B., Fornarini, S., Crestoni, M.E., Chiavarino, B., Carradori, S., Locatelli, M., Giusti, A.M., Simonetti, G., Vinci, G., Preti, R., Toniolo, C., Reverberi, M., Scarpari, M., Parroni, A., Abete, L., Natella, F., Di Sotto, A. A multi-methodological approach in the study of Italian PDO “Cornetto di Pontecorvo” red sweet pepper (2018) Food Chemistry, 255, 120-131.

2. Cevatemre, B., Erkisa, M., Aztopal, N., Karakas, D., Alper, P., Tsimplouli, C., Sereti, E., Dimas, K., Armutak, E.I.I., Gurevin, E.G., Uvez, A., Mori, M., Berardozzi, S., Ingallina, C., D’Acquarica, I., Botta, B., Ozpolat, B., Ulukaya, E. A promising natural product, pristimerin, results in cytotoxicity against breast cancer stem cells in vitro and xenografts in vivo through apoptosis and an incomplete autopaghy in breast cancer. Pharmacological Research (2018), 129, 500-514.

3. Mascarello, A., Orbem Menegatti, A.C., Calcaterra, A., Martins, P.G.A., Chiaradia-Delatorre, L.D., D’Acquarica, I., Ferrari, F., Pau, V., Sanna, A., De Logu, A., Botta, M., Botta, B., Terenzi, H., Mori, M. Naturally occurring Diels-Alder-type adducts from Morus nigra as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B. European Journal of Medicinal Chemistry 2017, 144, 277-288

4. Spallotta, F., Cencioni, C., Atlante, S., Garella, D., Cocco, M., Mori, M., Mastrocola, R., Kuenne, C., Guenther, S., Nanni, S., Azzimato, V., Zukunft, S., Kornberger, A., Sürün, D., Schnütgen, F., Von Melchner, H., Di Stilo, A., Aragno, M., Braspenning, M., Van Criekinge, W., De Blasio, M.J., Ritchie, R.H., Zaccagnini, G., Martelli, F., Farsetti, A., Fleming, I., Braun, T., Beiras-Fernandez, A., Botta, B., Collino, M., Bertinaria, M., Zeiher, A.M., Gaetano, C. Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells from Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation (2018) Circulation Research, 122 (1),31-46.

5. Calcaterra, A., Iovine, V., Botta, B., Quaglio, D., D’Acquarica, I., Ciogli, A., Iazzetti, A., Alfonsi, R., Lospinoso Severini, L., Infante, P., Di Marcotullio, L., Mori, M., Ghirga, F. Chemical, computational and functional insights into the chemical stability of the Hedgehog pathway inhibitor GANT61 (2018) Journal of Enzyme Inhibition and Medicinal Chemistry, 33 (1), pp. 349-358.

6. Al Sharif, M., Alov, P., Vitcheva, V., Diukendjieva, A., Mori, M., Botta, B., Tsakovska, I., Pajeva, I. Natural modulators of nonalcoholic fatty liver disease: Mode of action analysis and in silico ADME-Tox prediction. Toxicology and Applied Pharmacology 2017, 337, 45-66.

7. Mori, M., Tottone, L., Quaglio, D., Zhdanovskaya, N., Ingallina, C., Fusto, M., Ghirga, F., Peruzzi, G., Crestoni, M.E., Simeoni, F., Giulimondi, F., Talora, C., Botta, B., Screpanti, I., Palermo, R. Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia. Scientific Reports 2017, 7, 2213.

8. Ghirga, F., Bonamore, A., Calisti, L., D’Acquarica, I., Mori, M., Botta, B., Boffi, A., Macone, A. Green routes for the production of enantiopure benzylisoquinoline alkaloids. International Journal of Molecular Sciences 2017, 18 (11), 2464.

9. Pingwara, R., Witt-Jurkowska, K., Ulewicz, K., Mucha, J., Tonecka, K., Pilch, Z., Taciak, B., Zabielska-Koczywas, K., Mori, M., Berardozzi, S., Botta, B., Rygiel, T.P., Krol, M. Interferon lambda 2 promotes mammary tumor metastasis via angiogenesis extension and stimulation of cancer cell migration. Journal of Physiology and Pharmacology 2017, 68 (4), 573-583.

10. Ingallina, C., Costa, P.M., Ghirga, F., Klippstein, R., Wang, J.T., Berardozzi, S., Hodgins, N., Infante, P., Pollard, S.M., Botta, B., Al-Jamal, K.T. Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro. Nanomedicine 2017, 12 (7), 711-728.

11. Alfonsi, R., Botta, B., Cacchi, S., Di Marcotullio, L., Fabrizi, G., Faedda, R., Goggiamani, A., Iazzetti, A., Mori, M. Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway. Journal of Medicinal Chemistry 2017, 60 (4), 1496-1477.

12. Aiello, F., Balzano, F., Ghirga, F., D’Acquarica, I., Botta, B., Uccello-Barretta, G., Quaglio, D. First detection of a Ruthenium-carbene-resorc[4]arene complex during the progress of a metathesis reaction. EUR Journal of Organic Chemistry 2017, 17, 2407-2415.

13. Evain-Bana, E., Schiavo, L., Bour, C., Lanfranchi, D-A, Berardozzi, S., Ghirga, F., Bagrel, D., Botta, B., Hanquet, G., Mori, M. Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases. Journal of enzyme inhibition and medicinal chemistry 2017, 32(1),113-118.

14. Zwergel, C., Czepukojc, B., Evain-Bana, E., Xu, Z., Stazi, G., Mori, M., Patsilinakos, A., Mai, A., Botta, B., Ragno, R., Bagrel, D., Kirsch, G., Meiser, P., Jacob, C., Montenarh, M., Valente, S. Novel coumarin- and quinolinone-based polycycles as cell division cycle 25-A and -C phosphatases inhibitors induce proliferation arrest and apoptosis in cancer cells. European Journal of Medicinal Chemistry 2017, 134, 316-333.

15. Sobolev, A.P., Mannina, L., Aru, V., Bellomaria, A., Bertocchi, F., Botta, B., Cagliani, L.R., Caligiani, A., Capozzi, F., Çela, D., Marincola, F.C., Ciampa, A., Del Coco, L., Consonni, R., Corsaro, C., Delfini, M., Di Tullio, V., Fanizzio, F.P., Gallo, V., Ghirga, F., Gianferri, R., Girellio, C.R., Ingallina, C., Laghi, L., Latronico, M., Longobardi, F., Luchinat, C., Mallamace, D., Mammi, S., Mandaliti, W., Marini, F., Mastrorilli, P., Mazzei, P., Miccheli, A., Micozzio, A., Miloneo, S., Mucci, A., Nepravishta, R., Paci, M., Palisi, A., Piccolo, A., Picone, G., Proietti, N., Randazzo, A., Righi, V., Rotondo, A., Salvo, A., Savorani, F., Scano, P., Schievano, E., Sciubba, F., Tenori, L., Trimigno, A., Turano, P., Vasi, S., Capitani, D. NMR applications in food analysis: Part A (2017) Analytical Chemistry: Developments, Applications and Challenges in Food Analysis, pp. 157-253.

16. Proietti, N., Capitani, D., Aru, V., Bellomaria, A., Bertocchi, F., Botta, B., Cagliani, L.R., Caligiani, A., Capozzi, F., Çela, D., Marincola, F.C., Ciampa, A., Coco, L.D., Consonni, R., Corsaro, C., Delfini, M., Fanizzio, F.P., Gallo, V., Ghirga, F., Gianferri, R., Girellio, C.R., Ingallina, C., Laghi, L., Latronico, M., Longobardi, F., Luchinat, C., Mallamace, D., Mammi, S., Mandaliti, W., Mannina, L., Marini, F., Mastrorilli, P., Mazzei, P., Miccheli, A., Micozzio, A., Miloneo, S., Mucci, A., Nepravishta, R., Paci, M., Palisi, A., Sobolev, A.P., Piccolo, A., Picone, G., Randazzo, A., Righi, V., Rotondo, A., Salvo, A., Savorani, F., Scano, P., Schievano, E., Sciubba, F., Tenori, L., Trimigno, A., Turano, P., Vasi, S., Tullio, V.D. NMR applications in food analysis: Part B (2017) Analytical Chemistry: Developments, Applications and Challenges in Food Analysis, pp. 255-296.

17. Iovine, V., Benni, I., Sabia, R., D’Acquarica, I., Fabrizi, G., Botta, B., Calcaterra, C. Total Synthesis of (±)-Kuwanol E. Journal of Natural Product 2016, 79 (10), pp. 2495-2503.

18. Cevatemre, B., Botta, B., Mori, M., Berardozzi, S., Ingallina, C., Ulukaya, E. The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro. Chemico-Biological Interactions 2016, 260, pp. 248-255.

19. Infante, P., Alfonsi, R., Ingallina, C., Quaglio, D., Ghirga, F., D’Acquarica, I., Di Magno, L., Canettieri, G., Screpanti, I., Gulino, A., Botta, B., Mori, M., Di Marcotullio, L. Inhibition of Hedgehog-dependent tumors and cancer stem cells by a newly identified naturally occurring chemotype. Cell Death & Disease 2016, 7, e2376.

20. Ingallina, C., Rinaldi, F., Bogni, A., Ponti, J., Passeri, D., Reggente, M., Rossi, M., Kinsner-Ovaskainen, A.; Mehn, D., Rossi, F., Botta, B., Carafa, M., Marianecci, C. Niosomal approach to brain delivery: Development, characterization and in vitro toxicological studies. International journal of pharmaceutics 2016, 511 (2), pp.969-982.

21. Barretta, G. U., Balzano, F., Aiello, F., Nardelli, F., Ciogli, A., Calcaterra, A., Botta, B. Covalently assembled resorcin[4]arenes and molecular tweezers: a chiral recognition rationale by NMR. Supramolecular chemistry 2016, 21 (7-8), pp. 647-655.

22. Ghirga, F., Quaglio, D., Ghirga, P., Berardozzi, S., Zappia, G., Botta, B., Mori, M., D’Acquarica, I. Occurrence of Enantioselectivity in Nature: The Case of (S)-Norcoclaurine. Chirality 2016, 28 (3), pp. 169-180.

23. Comba, A., Ainnada, L. L., Tolosa, E. J., Iguchi, E., Marks, D. L., Messler, M. V., Silva, R., Fernandez-Barrena, M. G., Enriquez-Hesles, E., Vrabel, A. L., Botta, B., Di Marcotulio, L., Ellenrieder, V., Eynard, A. R., Pasqualini, M. E., Fernandez-Zapico, M. E. Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid. Journal of biological chemistry 2016, 291 (4), pp. 1933-1947.

24. Bonamore, A., Calisti, L., Calcaterra, A., Ismail, O.H., Gargano, M., D’Acquarica, I., Botta, B., Boffi, A., Macone, A. A Novel Enzymatic Strategy for the Synthesis of Substituted Tetrahydroisoquinolines. Chemistry Select 2016, 1 (8), pp. 1933-1947.

25. Cirigliano, A., Stirpe, A., Menta, S., Mori, M., Dell’Edera, D., Pick, E., Negri, R., Botta, B., Rinaldi, T. Yeast as a tool to select inhibitors of the cullin deneddylating enzyme Csn5. Journal of enzyme inhibition and medicinal chemistry 2016, 31 (6), pp. 1632-1637.

26. Navakauskiene, R., Mori, M., Christodoulou, M. S., Zentelyte, A., Botta, B., Dalla Via, L., Ricci, F., Damia, G., Passarella, D., Zilio, C., Martinet, N. Histone demethylating agents as potential S-adenosyl-L-methionine-competitors. Medicinal Chemical Communications 2016, 7 (6), pp. 1245-1255.

27. Mascarello, A., Chiaradia-Delatorre, L. D., Mori, M., Terenzi, H., Botta, B. Mycobacterium tuberculosis-Secreted Tyrosine Phosphatases as Targets Against Tuberculosis: Exploring Natural Sources in Searching for New Drugs. Current pharmaceutical design 2016, 22 (12), pp. 1561-1569.

28. D’Acquarica, I., Ghirga, F., Ingallina, C., Quaglio, D., Zappia, G., Uccello-Barretta, G., Balzano, F., Botta, B. Resorc[4]arenes as preorganized synthons for surface recognition and host-guest chemistry. In book: Calixarenes and Beyond 2016, pp. 175-193.

29. Iovine, V., Mori, M., Calcaterra, A., Berardozzi, S., Botta, B. One Hundred Faces of Cyclopamine. Current pharmaceutical design 2016, 22 (12), pp. 1658-1681.

30. D’Acquarica, I., Ghirga, F., Quaglio, D., Cerreto, A., Ingallina, C., Tafi, A., Botta, B. Molecular Recognition of Natural Products by Resorc[4]arene Receptors. Current pharmaceutical design (2016), 22 (12), pp. 1715-1729.

31. Khan, M. I., Sobocinska, A. A., Czarnecka, A. M., Krol, M., Botta, B., Szczylik, C. The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory. Current pharmaceutical design 2016, 22 (12), pp. 1756-1766.

32. Ingallina, C., D’Acquarica, I., Monache, G.D., Ghirga, F., Quaglio, D., Ghirga, P., Berardozzi, S., Markovic, V., Botta, B., The pictet-spengler reaction still on stage. Current Pharmaceutical Design 2016, 22 (12), pp. 1808-1850.

33. Esposito, F., Tintori, C., Martini, R., Christ, F., Debyser, Z., Ferrarese, R., Cabiddu, G., Corona, A., Ceresola, E. R., Calcaterra, A., Iovine, V., Botta, B., Clementi, M., Canducci, F., Botta, M., Tramontano, E. Kuwanon-L as a New Allosteric HIV-1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation. ChemBioChem 2015, 16 (17), pp. 2507-2512.

34. Martins, P. G. A., Mori, M., Chiaradia-Delatorre, L. D., Menegatti, A. C. O., Mascarello, A., Botta, B., Benitez, J., Gambino, D., Terenzi, H. Exploring Oxidovanadium(IV) Complexes as YopH Inhibitors: Mechanism of Action and Modeling Studies. ACS Medicinal Chemistry Letters 2015, 6 (10), pp. 1035-1040.

35. Christodoulou, M. S., Mori, M., Pantano, R., Alfonsi, R., Infante, P., Botta, M., Damia, G., Ricci, F., Sotiropoulou, P. A., Liekens, S., Botta, B., Passarella, D. Click Reaction as a Tool to Combine Pharmacophores: The Case of Vismodegib. ChemPlusChem 2015, 80(6), pp. 938-943.

36. Infante, P., Alfonsi, R., Botta, B., Mori, M., Di Marcotullio, L. Targeting Gli factors to inhibit the Hedgehog pathway. Trends in Pharmacological Sciences 2015, 36(8), pp. 547-558.
 
37. Infante, P., Mori, M., Alfonsi, R., Ghirga, F., Aiello, F., Toscano S., Ingallina C., Siler M., Cucchi D., Po A., Miele E., D’Amico D., Canettieri, G., De Smaele, E., Ferretti, E., Screpanti, I., Uccello Barretta, G., Botta, M., Botta, B., Gulino, A., and Di Marcotullio, L. Gli1/DNA interaction is a druggable target for Hedgehog‐dependent tumors. EMBO Journal 2015 34(2), pp. 200-217.

38. Uccello-Barretta, G., Balzano, F., Aiello, F., Vanni, L., Mori, M., Menta, S., Calcaterra, A., Botta, B.. Hydrolytic inhibition of α-chymotrypsin by 2,8,14,20-tetrakis(d-leucyl-d-valinamido) resorc[4]arenecarboxylic acid: a spectroscopic NMR and computational combined approach. Organic & Biomolecular Chemistry 2015, 13(3), pp. 916-924.