Leishmaniasis are a complex of parasitic diseases caused by different species of the protozoan belonging to the genus Leishmania. They are transmitted by vectors belonging to the genus Phlebotomus in the Old World and the genus Lutzomyia in the New World. Leishmaniasis is an endemic disease, present in 88 countries. It is estimated that 12 million people in the world are affected. An antileishmanial vaccine is not yet on the market, the therapy consists of chemotherapy drugs, but they have many disadvantages: high side effects and toxicity, a price not accessible to most people affected, and especially the development of resistance. The research is therefore aimed at the continuous development of new therapies. In this regard, in this study, a semisynthetic compound, RC-106, already known for its strong antitumor activity, was investigated. The research has also focused on two hydroxy derivatives of this drug, PV172 and PV174, trying to provide a biological screening of the molecules. RC-106 and its analogues PV172 and PV174 have shown remarkable activity against the promastigote forms of Leishmania chagasi. The cells exposed to the three drugs showed morphological and mobility changes. The same molecules were then very toxic against the murine macrophage cell line Raw 264.7, so the analysis performed on the amastigote form of the parasite requires further studies. This research highlights the molecules RC-106, PV172 and PV174 as potential new compounds in the treatment of leishmaniasis, but further new studies need to be developed. Leishmaniasis are a complex of parasitic diseases caused by different species of the protozoan belonging to the genus Leishmania. They are transmitted by vectors belonging to the genus Phlebotomus in the Old World and the genus Lutzomyia in the New World. Leishmaniasis is an endemic disease, present in 88 countries. It is estimated that 12 million people in the world are affected. An antileishmanial vaccine is not yet on the market, the therapy consists of chemotherapy drugs, but they have many disadvantages: high side effects and toxicity, a price not accessible to most people affected, and especially the development of resistance. The research is therefore aimed at the continuous development of new therapies. In this regard, in this study, a semisynthetic compound, RC-106, already known for its strong antitumor activity, was investigated. The research has also focused on two hydroxy derivatives of this drug, PV172 and PV174, trying to provide a biological screening of the molecules. RC-106 and its analogues PV172 and PV174 have shown remarkable activity against the promastigote forms of Leishmania chagasi. The cells exposed to the three drugs showed morphological and mobility changes. The same molecules were then very toxic against the murine macrophage cell line Raw 264.7, so the analysis performed on the amastigote form of the parasite requires further studies. This research highlights the molecules RC-106, PV172 and PV174 as potential new compounds in the treatment of leishmaniasis, but further new studies need to be developed.
Le Leishmaniosi sono un complesso di malattie parassitarie causate da specie differenti del protozoo appartenente al genere Leishmania. Esse sono trasmesse da vettori appartenenti al genere Phlebotomus nel Vecchio Mondo e il genere Lutzomyia nel Nuovo Mondo. La leishmaniosi è una malattia endemica, presente in 88 paesi. Si stima che 12 milioni di persone nel mondo ne siano affette. Un vaccino antileishmaniale non è ancora in commercio, la terapia è costituita da farmaci chemioterapici, ma che presentano molti svantaggi: elevati effetti collaterali e tossicità, un prezzo non accessibile alla maggior parte delle persone affette, e soprattutto lo sviluppo di resistenza. La ricerca è dunque volta al continuo sviluppo di nuove terapie. A tal proposito, in questo studio, è stato indagato un composto semisintetico, RC-106, già noto per la spiccata attività antitumorale. La ricerca si è concentrata anche su due derivati idrossilati di questo farmaco, PV172 e PV174, cercando di procurare uno screening biologico delle molecole. RC-106 e i suoi analoghi PV172 e PV174 hanno mostrato notevole attività contro le forme promastigote di Leishmania chagasi. Le cellule esposte ai tre farmaci hanno mostrato cambiamenti morfologici e di mobilità. Le stesse molecole sono poi risultate molto tossiche nei confronti della linea cellulare di macrofagi murini Raw 264.7, motivo per cui l’analisi effettuata sulla forma amastigote del parassita richiede ulteriori studi. Questa ricerca evidenzia le molecole RC-106, PV172 e PV174 come potenziali nuovi composti nel trattamento della leishmaniosi, ma ulteriori nuovi studi devono essere sviluppati.
Nuove naftalen-alchenil-piperidine come promettenti composti anti Leishmania
PAROLO, MADDALENA
2019/2020
Abstract
Leishmaniasis are a complex of parasitic diseases caused by different species of the protozoan belonging to the genus Leishmania. They are transmitted by vectors belonging to the genus Phlebotomus in the Old World and the genus Lutzomyia in the New World. Leishmaniasis is an endemic disease, present in 88 countries. It is estimated that 12 million people in the world are affected. An antileishmanial vaccine is not yet on the market, the therapy consists of chemotherapy drugs, but they have many disadvantages: high side effects and toxicity, a price not accessible to most people affected, and especially the development of resistance. The research is therefore aimed at the continuous development of new therapies. In this regard, in this study, a semisynthetic compound, RC-106, already known for its strong antitumor activity, was investigated. The research has also focused on two hydroxy derivatives of this drug, PV172 and PV174, trying to provide a biological screening of the molecules. RC-106 and its analogues PV172 and PV174 have shown remarkable activity against the promastigote forms of Leishmania chagasi. The cells exposed to the three drugs showed morphological and mobility changes. The same molecules were then very toxic against the murine macrophage cell line Raw 264.7, so the analysis performed on the amastigote form of the parasite requires further studies. This research highlights the molecules RC-106, PV172 and PV174 as potential new compounds in the treatment of leishmaniasis, but further new studies need to be developed. Leishmaniasis are a complex of parasitic diseases caused by different species of the protozoan belonging to the genus Leishmania. They are transmitted by vectors belonging to the genus Phlebotomus in the Old World and the genus Lutzomyia in the New World. Leishmaniasis is an endemic disease, present in 88 countries. It is estimated that 12 million people in the world are affected. An antileishmanial vaccine is not yet on the market, the therapy consists of chemotherapy drugs, but they have many disadvantages: high side effects and toxicity, a price not accessible to most people affected, and especially the development of resistance. The research is therefore aimed at the continuous development of new therapies. In this regard, in this study, a semisynthetic compound, RC-106, already known for its strong antitumor activity, was investigated. The research has also focused on two hydroxy derivatives of this drug, PV172 and PV174, trying to provide a biological screening of the molecules. RC-106 and its analogues PV172 and PV174 have shown remarkable activity against the promastigote forms of Leishmania chagasi. The cells exposed to the three drugs showed morphological and mobility changes. The same molecules were then very toxic against the murine macrophage cell line Raw 264.7, so the analysis performed on the amastigote form of the parasite requires further studies. This research highlights the molecules RC-106, PV172 and PV174 as potential new compounds in the treatment of leishmaniasis, but further new studies need to be developed.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12451