Imaging and Quantitative Detection of Lipid Droplets by Yellow Fluorescent Probes in Liver Sections of Plasmodium Infected Mice and Third Stage Human Cervical Cancer Tissues.

The diagnosis and prognosis of the disease associated with lipid irregularity are areas of extreme significance. In this direction, fluoranthene based yellow fluorescent probes (FLUN-550, FLUN-552, FLUN-547) were designed and synthesized by conjugating the ethanolamine headgroup of the phospholipid phosphatidyl-ethanolamine present in biological membranes. Owing to unique photophysical properties and aqueous compatibility, these probes were successfully employed for staining lipid droplets (LDs) in preadipocytes and Leishmania donovani promastigotes. Furthermore, using the fluorescent probes FLUN-550 and FLUN-552 we successfully imaged and quantitatively detected the excess accumulation of lipids in a liver section of Plasmodium yoelii MDR infected mice (3- to 4-fold) and the tissue sections of third stage human cervical cancer patients (1.5- to 2-fold) compared to normal tissues. To the best of our knowledge, this is the first report of yellow fluorescent probes for imaging and quantitative detection of LDs in human cervical cancer tissues. These new yellow fluorescent lipid probes (FLUN-550 and FLUN-552) showed great potential for diagnosis of cervical cancer patients.

Artemisinin Derivatives and Synthetic Trioxane Trigger Apoptotic Cell Death in Asexual Stages of Plasmodium.

Although over the last 15 years, prevalence of malaria became reduced by over half but developing resistance against artemisinin derivatives and its combinations, which are only ray of hope to treat resistant malaria set back the control efforts and the key hinderence to achieve the goal of malaria elimination till 2030. In spite these artemisinins are precious antimalarials, their action mechanism is yet to be fully understood. Reactive oxygen species (ROS) produces by cleavage of endoperoxide bridge of artemisinin derivatives are known to be its antimalarial efficacy. Since ROS could induce apoptosis, here we had explored the effect of artemisinin derivatives on apoptotic machinery of malaria parasite, Plasmodium falciparum and its survival. We have studied the effect of a/ß arteether, artesunate and a synthetic 1, 2, 4 trioxane on mitochondria, caspase activity and DNA during asexual blood stages of Plasmodium falciparum 3D7. Results have shown that cleavage of peroxide bridge of artemisinin derivatives and 1,2,4 trioxane generate reactive oxygen species which depolarize mitochondrial membrane potential and make it permeable which further followed by activation of caspase like enzyme and DNA fragmentation, which are hallmark of apoptotic cell death. These findings suggest that artemisinin derivatives and synthetic trioxane induce apoptosis like phenomena in erythrocytic stage of malaria parasite; Plasmodium falciparum.

Substituted carbamothioic amine-1-carbothioic thioanhydrides as novel trichomonicidal fungicides: Design, synthesis, and biology.

Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 µM and 32.46-735.20 µM against MTZ-susceptible and -resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50-240.38 µM. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance.