Sensitivity of antimony(III)-sensitive and -resistant MRPA-overexpressing and AQP1-mutated Leishmania strains towards novel organoantimony(V) and organobismuth(V) complexes and their effect on DNA and membrane integrity

Title : Sensitivity of antimony(III)-sensitive and -resistant MRPA-overexpressing and AQP1-mutated Leishmania strains towards novel organoantimony(V) and organobismuth(V) complexes and their effect on DNA and membrane integrity

Abstract:

The aim the present study was to investigate the impact of novel pentavalent organobismuth and organoantimony complexes on membrane integrity and their interaction with DNA, activity against Sb(III)-sensitive and -resistant Leishmania strains and toxicity in mammalian peritoneal macrophages. Ph 3M(L) 2 type complexes were synthesized, where M = Sb(V) or Bi(V) and L = deprotonated 3-(dimethylamino) benzoic acid or 2-acetylbenzoic acid. Both organobismuth(V) and organoantimony(V) complexes exhibited efficacy at micromolar concentrations against Leishmania amazonensis and L. infantum but only the later ones demonstrated biocompatibility. Ph 3Sb(L1)2 and Ph 3Bi(L1) 2 demonstrated distinct susceptibility profiles compared to inorganic Sb(III)-resistant strains of MRPA-overexpressing L. amazonensis and AQP1- mutated L. guyanensis. These complexes were able to permeate the cell membraneand interact with the Leishmania DNA, suggesting that this effect may contribute to the parasite growth inhibition via apoptosis. Taken altogether, our data substantiate the notion of a distinct mechanism of uptake pathway and action in Leishmania for these organometallic complexes, distinguishing them from the conventional inorganic antimonial drugs.

Keywords: Antimony and bismuth, drug resistance, leishmaniasis, mechanism of action, membrane permeability and DNA interaction, organometallics.

Biography:

Dr. Arshad Islam studied Biochemistry and obtained his PhD in 2014. He worked as Assistant Professor at the International Islamic University, Islamabad, and currently serves as Assistant Professor and Consultant Chemical Pathologist at Lady Reading Hospital, Peshawar. He oversees diagnostic services in chemical pathology and molecular biology, and contributes to clinical research and postgraduate training. He has authored over 40 peer-reviewed publications and recently published a book on nanobiotechnology with CRC Press. His research interests include clinical diagnostics, infectious diseases, and translational nanomedicine. He is actively involved in academic committees and healthcare policy development.