Repurposing of conformationally-restricted cyclopentane-based AKT-inhibitors leads to discovery of potential and more selective antileishmanial agents than miltefosine.

Conformational restriction was addressed towards the development of more selective and effective antileishmanial agents than currently used drugs for treatment of Leishmania donovani; the causative parasite of the fatal visceral leishmaniasis. Five types of cyclopentane-based conformationally restricted miltefosine analogs that were previously explored in literature as anticancer AKT-inhibitors were reprepared and repurposed as antileishmanial agents. Amongst, positions-1 and 2 cis-conformationally-restricted compound 1a and positions-2 and 3 trans-conformationally-restricted compound 3b were highly potent eliciting sub-micromolar IC values for inhibition of infection and inhibition of parasite number compared with the currently used miltefosine drug that showed low micromolar IC values for inhibition of infection and inhibition of parasite number.

Rational repurposing, synthesis, and studies of chromone-peptidyl hybrids as potential agents against .

A chromone-peptidyl hybrids series was synthesised and rationally repurposed towards identification of potential antileishmanial hits against visceral leishmaniasis. Three hybrids , , and showed potential IC values (9.8, 10, and 12 µM, respectively) which were comparable to erufosine IC (9.

Design, synthesis, and study of novel phenethyl-based antitumor phospholipids downregulating p38 mitogen-activated protein kinase.

Phenethyl-based edelfosine-analogs with saturated, monounsaturated, or polyunsaturated alkoxy substituents on phenyl ring were designed as novel antitumor lipids modulating p38 MAPK. Evaluation of the synthesised compounds against nine panels of diverse cancer cells presented saturated and monounsaturated alkoxy-substituted derivatives as the most active than other derivatives. In addition, -substituted compounds were more active than - or -substituted compounds.

Synthesis and Biological Evaluation of -Aminoalkyl-Hispidol Analogs as Multifunctional Monoamine Oxidase-B Inhibitors towards Management of Neurodegenerative Diseases.

Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells' death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline: 5,6,7-Trimethoxyflavan derivatives as novel potential anticancer agents modulating hippo signaling pathway.

Scaffold hopping of N-benzyl-3,4,5-trimethoxyaniline afforded 5,6,7-trimethoxyflavan derivatives that were efficiently synthesized in four linear steps. As lung cancer is the most lethal cancer, twenty-three synthesized compounds were evaluated against a panel of lung cancer cells. Amongst, compounds 8q and 8e showed interesting activity.

Design, synthesis, and repurposing of O-aminoalkyl-sulfuretin analogs towards discovery of potential lead compounds as antileishmanial agents.

Up to date, there are still significantly unmet clinical needs for treatment of the fatal visceral leishmaniasis; a neglected tropical disease. Herein, a recently reported antileishmanial hit sulfuretin analog suffering from a low potency and a problematic aqueous solubility that hindered further development was used as a starting point. A mitigation rational via incorporation of O-aminoalkyl moiety suggest structures analogous to literature-known compounds as cholinesterase inhibitors.

Bestatin analogs-4-quinolinone hybrids as antileishmanial hits: Design, repurposing rational, synthesis, in vitro and in silico studies.

Amongst different forms of leishmaniasis, visceral leishmaniasis caused by L. donovani is highly mortal. Identification of new hit compounds might afford new starting points to develop novel therapeutics.

Different treatment protocols for different pulpal and periapical diagnoses of 72 cracked teeth.

Introduction: The treatment plan for cracked teeth depends on the extent of the crack. A tooth with an extensive crack of long duration may be more likely to require root canal treatment. The purpose of this study was to analyze the characteristics of cracked teeth and to assess the outcome of different treatment protocols depending on the pulpal and periapical diagnoses.