<i>In-vivo</i> anti-epileptic study of newly synthesized pregabalin derivatives based on docking studies

The goal of the present study is to examine pretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu) complexes on the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in mice. To achieve the goal, a molecular docking study of analogues was carried out on a specific molecular target, such as the alpha-2δ receptor (PDB ID: 6ND9); which revealed the significant binding affinity of the analogs to their respective target. Based on the docking information, all pregabalin derivatives were synthesized and in-vivo antiepileptic effect was confirmed by applying the PTZ model that prioritized the most crucial significant points responsible for biological activity. The test compounds markedly increased the latency of the first seizure and reduced the frequency of seizures throughout the body and frequent spinning and jumps. Additionally, treatment with pregabalin derivatives in mice that received PTZ significantly reduced the duration of seizures and seizure score. However, it increased the survival rate of the mice. Since the newly synthesized compounds were more active as compared to the parent drug in some respects; therefore, the expansion of the project can be planned to explore clinical side of the drugs in the future. Docking studies of Schiff bases and derivatives of Pregabalin along with their Zn and Cu metal complexesPretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu)PTZ Model of epilepsyObservation of different parameters including; the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in miceNewly synthesized compounds were more active as compared to the parent drug Docking studies of Schiff bases and derivatives of Pregabalin along with their Zn and Cu metal complexes Pretreatment with Schiff bases and derivatives of pregabalin along with their metal (Zn and Cu) PTZ Model of epilepsy Observation of different parameters including; the severity of epilepsy, latency time, duration of convulsions, seizure score and survival rate in mice Newly synthesized compounds were more active as compared to the parent drug</p

Table_1_Molecular Typing of ST239-MRSA-III From Diverse Geographic Locations and the Evolution of the SCCmec III Element During Its Intercontinental Spread.PDF

<p>ST239-MRSA-III is probably the oldest truly pandemic MRSA strain, circulating in many countries since the 1970s. It is still frequently isolated in some parts of the world although it has been replaced by other MRSA strains in, e.g., most of Europe. Previous genotyping work (Harris et al., 2010; Castillo-Ramírez et al., 2012) suggested a split in geographically defined clades. In the present study, a collection of 184 ST239-MRSA-III isolates, mainly from countries not covered by the previous studies were characterized using two DNA microarrays (i) targeting an extensive range of typing markers, virulence and resistance genes and (ii) a SCCmec subtyping array. Thirty additional isolates underwent whole-genome sequencing (WGS) and, together with published WGS data for 215 ST239-MRSA-III isolates, were analyzed using in-silico analysis for comparison with the microarray data and with special regard to variation within SCCmec elements. This permitted the assignment of isolates and sequences to 39 different SCCmec III subtypes, and to three major and several minor clades. One clade, characterized by the integration of a transposon into nsaB and by the loss of fnbB and splE was detected among isolates from Turkey, Romania and other Eastern European countries, Russia, Pakistan, and (mainly Northern) China. Another clade, harboring sasX/sesI is widespread in South-East Asia including China/Hong Kong, and surprisingly also in Trinidad & Tobago. A third, related, but sasX/sesI-negative clade occurs not only in Latin America but also in Russia and in the Middle East from where it apparently originated and from where it also was transferred to Ireland. Minor clades exist or existed in Western Europe and Greece, in Portugal, in Australia and New Zealand as well as in the Middle East. Isolates from countries where this strain is not epidemic (such as Germany) frequently are associated with foreign travel and/or hospitalization abroad. The wide dissemination of this strain and the fact that it was able to cause a hospital-borne pandemic that lasted nearly 50 years emphasizes the need for stringent infection prevention and control and admission screening.</p