Binding selectivity analysis of AURKs inhibitors through molecular dynamics simulation studies.

Aurora kinases (AURKs) have been identified as promising biological targets for the treatment of cancer. In this study, molecular dynamics simulations were employed to investigate the binding selectivity of three inhibitors (HPM, MPY, and VX6) towards AURKA and AURKB by predicting their binding free energies. The results show that the inhibitors HPM, MPY, and VX6 have more favorable interactions with AURKB as compared to AURKA. The binding energy decomposition analysis revealed that four common residue pairs (L139, L83), (V147, V91), (L210, L154), and (L263, L207) showed significant binding energies with HPM, MPY, and VX6, hence responsible for the binding selectivity of AURKA and AURKB to the inhibitors. The MD trajectory analysis also revealed that the inhibitors affect the dynamic flexibility of protein structure, which is also responsible for the partial selectivity of HPM, MPY, and VX6 towards AURKA and AURKB. As expected, this study provides useful insights for the design of potential inhibitors with high selectivity for AURKA and AURKB.

Optimization of process variables for increased production of lovastatin in Aspergillus terreus PU-PCSIR1 and its characterization.

During intrinsic cholesterol formation 3-hydroxy-3-methylgutaryl coenzyme A reductase (HMGCR) converts HMGCoA to mevalonate, in biosynthetic cascade of cholesterol. Statins, competitive inhibitors of HMGCR, now-a-days commonly used to lower the blood-cholesterol level in the hyper-cholesterolemic patients. Lovastatin, one of the most potent natural statins, was produced from wild-type indigenous isolate Aspergillus terreus PU-PCSIR-1, through solid state fermentation (SSF). This study was carried out to investigate different parameters influencing lovastatin production such as pH, carbon source, nitrogen source and media components etc. Each parameter was investigated separately to optimize lovastatin production. Maximum yield of 2860mg/Kg of total lovastatin, comprising 1700 and 1160mg/Kg of hydroxy and lactone forms respectively, was achieved after incubating for 14 days, pH 5.5 and at 28°C. The integrity of biotechnologically-produced lovastatin was analyzed using high performance liquid chromatography (HPLC). Lovastatin was purified by preparative HPLC, and was characterized by FT-IR and LC-MS analyses. The study revealed that A. terreus PU-PCSIR-1 has been proved to be a potent strain for the production of lovastatin that has great pharmaceutical and commercial applications.

Staphylococcus aureus carrying lukS/F Panton-Valentine Leukocidin (PVL) toxin genes in hospitals of Lahore city.

INTRODUCTION: Panton Valentine-Leukocidin (PVL) toxin is secreted by Staphylococcus aureus and is mostly associated with skin and soft tissue infections (SSTI). This study aims to find out the prevalence of lukS/F-PV gene, which encode PVL toxin from strains of SSTI, burn wounds and nasal colonizers of out-patients and to measure the antimicrobial susceptibility of S. aureus isolates. METHODOLOGY: This is an analytical observational cross-section study and was conducted from July 2014 to June 2015 at four tertiary care hospitals and PCSIR Laboratories Complex, Lahore, Pakistan. A total of 376 random clinical swabs were collected from SSTI (n = 179), nasal nares (n = 134) and burn wounds (n = 63) from out-patients' departments (OPD). The specimens were cultured on nutrient and mannitol salt agar (MSA) and the organism was identified by catalase, coagulase, and DNase tests. Antimicrobial susceptibility, methicillin, inducible clindamycin, and high-level mupirocin (HLMR) resistance were determined as per CLSI guidelines. Molecular identification of mecA and lukS/F-PV genes was performed by PCR. RESULTS: We isolated 127 S. aureus, where 41 (32.3%) were MRSA and 86 (67.7%) were MSSA. All MRSA carried mecA gene whereas lukS/F-PV gene was found in 21 MRSA and 31 MSSA strains. Overall, a high antimicrobial resistance was found against MRSA and lukS/F-PV positive MSSA. Inducible clindamycin and high-level mupirocin resistance (HLMR) was 23.6% and 19.5% respectively. CONCLUSIONS: A high rate of PVL toxin gene was detected among S. aureus strains and a high prevalence of antimicrobial resistant strains was observed.