New pyrazolylpyrazoline derivatives as dual acting antimalarial-antileishamanial agents: synthesis,biological evaluation and molecular modelling simulations

Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of in vivo antimalarial activities of new pyrazolylpyrazoline derivatives against Plasmodium berghei infected mice. Further evaluation of 5b and 6a against chloroquine-resistant strain (RKL9) of P. falciparum showed higher potency than chloroquine. In vitro antileishmanial activity testing against Leishmania aethiopica promastigote and amastigote forms indicated that 5b, 6a and 7b possessed promising activity compared to miltefosine and amphotericin B deoxycholate. Moreover, antileishmanial activity reversal of the active compounds via folic and folinic acids showed comparable results to the positive control trimethoprim, indicating an antifolate mechanism via targeting leishmanial DHFR and PTR1. The compounds were non-toxic at 125, 250 and 500 mg/kg. In addition, docking of the most active compound against putative malarial target Pf-DHFR-TS and leishmanial PTR1 rationalised the observed activities. Molecular dynamics simulations confirmed a stable and high potential binding of 7a against leishmanial PTR1.     

Skeletal structure as taxonomic tool for identification of mullet species (Teleostei: Mugilidae) from Aceh waters,Indonesia

Many members of the mullets (family Mugilidae) are very similar morphologically, hence the possibility of taxonomic misidentification. This study involved the use of skeleton structure to distinguish four species of mullets, including Cremugil crenilabis, Liza macrolepis, Moolgarda engelii, and Mugil cephalus, harvested from Aceh waters, Indonesia. The mullets samples were collected from 10 locations, and a total of 10 samples were taken randomly as representatives of each species. The skeletal sample was prepared using the dry method. The results showed the presence of 8 pairs of ribs in C. crenilabis and L. macrolepis, while M. engelii had 9, with 10 in M. cephalus. In addition, the origin of the haemal canal of C. crenilabis is at the 12th vertebrae, extends to the 23rd, while for the other three species it starts at the 10th and extends to the 23rd. In addition, C. crenilabis possesses 12 haemal canals, but the rest have 14. The haemal canal is present in the last precaudal vertebrae of all specimens, except C. crenilabis, whose epural bone in the caudal skeleton is small and located far from the preural, while a larger and distinctly attached form is observed in the rest. Furthermore, L. macrolepis possess a pair of diapophyses, which laterally extend in the 2nd vertebrae. This bone is absent in the three other species. The presence of diapophyses, the number of ribs and haemal canals and the location of the epural bone in the caudal skeleton, and the condition of frontal attachment to the sphenotic are the important characters in distinguishing the four investigated species of mullets.     

Chemical screening identifies an extract from marine Pseudomonas sp.-PTR-08 as an anti-aging agent that promotes fission yeast longevity by modulating the Pap1–ctt1+ pathway and the cell cycle

Molecular Biology Reports - Aging is a degenerative process characterized by progressive deterioration of cellular components, ultimately resulting in mortality, in which massive accumulation of...