Arshad Islam
Universidade Federal de Minas Gerais, Brazil
Title: Pentavalent organoantimony and organobismuth complexes: evidence of interaction with DNA, membrane permeability and activity against leishmania strains resistant to inorganic antimony
Biography:
Dr. Arshad Islam, currently a postdoctoral research fellow at Universidade Federal de Minas Gerais – Brazil, has experience in inorganic chemistry, biological chemistry, medicinal chemistry, nano-biotechnology and molecular biology. He has been working on various research projects including synthesis and characterization of organometallic complexes, nanosystems, metal nanoparticles and their evaluation in in vitro and in vivo experimental models of leishmaniasis, cancer, bacterial infection and Chagas disease and also their interaction with various biomolecules involved in different metabolic pathways. He has published 7 scientific articles in international scientific journals of high impact and a book chapter. Dr. Islam has presented his research in several national and international conferences
Abstract:
In an effort to further investigate the potential of organoantimony(V) and organobismuth(V) complexes as antileishmanial agents, we report here new complexes with benzoic acid derivatives, their interaction with DNA, cytotoxicity and activities against amastigotes and Sb-sensitive and -resistant promastigotes from different Leishmania species. Four complexes of the Ph3M(L)2 type were synthesized and characterized, where M= Sb(V) or Bi(V) and L= deprotonated ligand of sodium salt of 3-(dimethylamino)benzoic acid (HL1) or 2-acetylbenzoic acid (HL2). The crystal and molecular structures of the complexes with L1 were determined by single crystal X-ray diffraction. An interaction was demonstrated between pX145 plasmid DNA and both organoantimony(V) and organobismuth(V), their complexes and the inorganic Sb(III). Ph3Sb(L1)2 and Ph3Sb(L2)2 were active against L. amazonensis and L. infantum promastigotes and intramacrophagic amastigotes in the range of 3.6-18 µM and showed selectivity index in the range of 2.1-3.9. Ph3Bi(L1)2 was more active against promastigotes (1.2-2.5 µM) than intramacrophagic amastigotes (3.8-11 µM), whereas Ph3Bi(L2)2 was inactive against the amastigote form. Ph3Sb(L1)2 and Ph3Bi(L1)2 showed no cross-resistance with inorganic Sb(III) in resistant MRPA-overexpressing L. amazonensis and AQP1-mutated L. guyanensis lines. Cytometric analysis using propidium iodide exhibited that Ph3Sb(L1)2 and Ph3Bi(L1)2 were able to permeate the cellular membrane. Our data taken altogether support the model of different mechanism of action and uptake pathway in Leishmania for these organometallic complexes, when compared to the conventional inorganic antimonial drugs.