Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies.

A series of semicarbazone, thiosemicarbazone, thiazole, and oxazole derivatives were designed, synthesized, and examined for monoamine oxidase inhibition using two isoforms, i.e., MAO-A and MAO-B. Among all the analogues, 3c and 3j possessed substantial activity against MAO-A with IC50 values of 5.619 ± 1.04 µM and 0.5781 ± 0.1674 µM, respectively. Whereas 3d and 3j were active against monoamine oxidase B with the IC50 values of 9.952 ± 1.831 µM and 3.5 ± 0.7 µM, respectively. Other derivatives active against MAO-B were 3c and 3g with the IC50 values of 17.67 ± 5.6 µM and 37.18 ± 2.485 µM. Moreover, molecular docking studies were achieved for the most potent compound (3j) contrary to human MAO-A and MAO-B. Kinetic studies were also performed for the most potent analogue to evaluate its mode of interaction with MAO-A and MAO-B.

Exploring Novel Pyridine Carboxamide Derivatives as Urease Inhibitors: Synthesis, Molecular Docking, Kinetic Studies and ADME Profile.

The rapid development of resistance by ureolytic bacteria which are involved in various life-threatening conditions such as gastric and duodenal cancer has induced the need to develop a new line of therapy which has anti-urease activity. A series of pyridine carboxamide and carbothioamide derivatives which also have some novel structures were synthesized via condensation reaction and investigated against urease for their inhibitory action. Among the series, 5-chloropyridine-2 yl-methylene hydrazine carbothioamide (Rx-6) and pyridine 2-yl-methylene hydrazine carboxamide (Rx-7) IC50 = 1.07 ± 0.043 µM, 2.18 ± 0.058 µM both possessed significant activity. Furthermore, molecular docking and kinetic studies were performed for the most potent inhibitors to demonstrate the binding mode of the active pyridine carbothioamide with the enzyme urease and its mode of interaction. The ADME profile also showed that all the synthesized molecules present oral bioavailability and high GI absorption.

An overview of viruses discovered over the last decades and drug development for the current pandemic.

Since the discovery of the yellow fever virus in 1901, thus far, two hundred nineteen viral species are recognized as human pathogens. Each year, the number of viruses causing infections in humans increases, triggering epidemics and pandemics, such as the current COVID-19 pandemic. Pointing to bats as the natural host, in 2019, a genome highly identical to a bat coronavirus (COVID-19) spread all over the world, and the World Health Organization (WHO) officially confirmed it as a pandemic. The virus mainly spreads through the respiratory tract, uses angiotensin-converting enzyme 2 (ACE2) as a receptor, and is characterized by symptoms of fever, cough, and fatigue. Antivirals and vaccines have provided improvements in some cases, but the discovery of a new and diverse variety of viruses with outbreaks has posed a challenge in timely treatments for medical scientists. Currently, few specific antiviral strategies are being used, and many of the effective antiviral drugs and reported active molecules are under vital exploration. In this review, with the details of viral diseases, we summarize the current attempts in drug development, epidemiology, and the latest treatments and scientific advancements to combat the COVID-19 epidemic. Moreover, we discuss ways to reduce epidemics and pandemics in the near future.