ABSTRACT
Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 µM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-µM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.
Subject(s)
Drug Repositioning , Leishmania donovani/drug effects , Leishmaniasis, Visceral/drug therapy , Methyltransferases/antagonists & inhibitors , Simeprevir/pharmacology , Drug Approval , Leishmania donovani/enzymologyABSTRACT
This paper reports the potential application of cadmium selenide (CdSe) quantum dots (QDs) in improving the microelectronic characteristics of Schottky barrier diode (SBD) prepared from a semiconducting material poly-(9,9-dioctylfluorene) (F8). Two SBDs, Ag/F8/P3HT/ITO and Ag/F8-CdSe QDs/P3HT/ITO, are fabricated by spin coating a 10 wt% solution of F8 in chloroform and 10:1 wt% solution of F8:CdSe QDs, respectively, on a pre-deposited poly(3-hexylthiophene) (P3HT) on indium tin oxide (ITO) substrate. To study the electronic properties of the fabricated devices, current-voltage (I-V) measurements are carried out at 25 °C in dark conditions. The I-V curves of Ag/F8/P3HT/ITO and Ag/F8-CdSe QDs/P3HT/ITO SBDs demonstrate asymmetrical behavior with forward bias current rectification ratio (RR) of 7.42 ± 0.02 and 142 ± 0.02, respectively, at ± 3.5 V which confirm the formation of depletion region. Other key parameters which govern microelectronic properties of the fabricated devices such as charge carrier mobility (µ), barrier height (Ïb), series resistance (Rs) and quality factor (n) are extracted from their corresponding I-V characteristics. Norde's and Cheung functions are also applied to characterize the devices to study consistency in various parameters. Significant improvement is found in the values of Rs, n, and RR by 3, 1.7, and 19 times, respectively, for Ag/F8-CdSe QDs/P3HT/ITO SBD as compared to Ag/F8/P3HT/ITO. This enhancement is due to the incorporation of CdSe QDs having 3-dimensional quantum confinement and large surface-to-volume area. Poole-Frenkle and Richardson-Schottky conduction mechanisms are also discussed for both of the devices. Morphology, optical bandgap (1.88 ± 0.5 eV) and photoluminescence (PL) spectrum of CdSe QDs with a peak intensity at 556 nm are also reported and discussed.
ABSTRACT
Acute myocardial infarction following coronary artery dissection during the post-partum period is a rare entity. Greater hemodynamic stress and hormonal changes increase the risk of developing a coronary artery dissection post-partum. Herein, we report the first case of a normotensive patient from Pakistan that presented with inferior wall myocardial infarction following 10-days postpartum due to right coronary artery dissection. This article highlights the importance of prompt diagnosis and subsequent life-saving treatment.