Synthesis, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities, and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide.

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of -12.9 kcal mol-1 and -9.8 kcal mol-1 respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be -10.1 kcal mol-1 and -8.9 kcal mol-1, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver-Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer's disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

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.

A review on versatile applications of blends and composites of CNC with natural and synthetic polymers with mathematical modeling.

Cellulose is world's most abundant, renewable and recyclable polysaccharide on earth. Cellulose is composed of both amorphous and crystalline regions. Cellulose nanocrystals (CNCs) are extracted from crystalline region of cellulose. The most attractive feature of CNC is that it can be used as nanofiller to reinforce several synthetic and natural polymers. In this article, a comprehensive overview of modification of several natural and synthetic polymers using CNCs as reinforcer in respective polymer matrix is given. The immense activities of CNCs are successfully utilized to enhance the mechanical properties and to broaden the field of application of respective polymer. All the technical scientific issues have been discussed highlighting the recent advancement in biomedical and packaging field.

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.