Syed Mohd. Danish Rizvi

Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment

Antibiotic resistance is a problem of deep scientific concern both in hospital and community settings. Rapid detection in clinical laboratories is essential for the judicious recognition of antimicrobial resistant organisms. Production of extended-spectrum β-lactamases (ESBLs) is a significant resistance-mechanism that impedes the antimicrobial treatment of infections caused by Enterobacteriaceae and is a serious threat to the currently available antibiotic armory. ESBLs are classified into several groups according to their amino acid sequence homology. Proper infection control practices and barriers are essential to prevent spread and outbreaks of ESBL producing bacteria. As bacteria have developed different strategies to counter the effects of antibiotics, the identification of the resistance mechanism may help in the discovery and design of new antimicrobial agents. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Hence, more expeditious diagnostic testing of ESBL-producing bacteria and the feasible modification of guidelines for community-onset bacteremia associated with different infections are prescribed.

Isolation, partial purification and evaluation of bioactive compounds from leaves of Ageratum houstonianum

The present study deals with the isolation and partial purification of bioactive compounds from the crude methanol extracts of the leaves of Ageratum houstonianum (Asteraceae). The quantification and the identification of compounds in the crude extract and active bands isolated by preparative TLC were accomplished using GC-MS analysis. The most important compounds identified in the crude extract and active bands (AB-1 and AB-2) were 6-acetyl-7-methoxy-2, 2-dimethylchromene, hexadecanoic acid and squalene, respectively. Crude extract and active bands (AB-1 and AB-2) were investigated for their antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, Bacillus subtilis, Bacillus cereus, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The crude extract, AB-1 and AB-2 showed maximum zone of inhibition (10-13 mm) against Staphylococcus epidermidis, however, the antibacterial potential of active bands was slightly higher as compared to the crude extract. Dose-dependant increase in antioxidant potential was noticed in crude extract as well as with both active bands measured by DPPH free radicals, ion chelation and total antioxidants capacity. Our study reports various bioactive compounds in the leaves of the A. houstonianum with significant antioxidant and antibacterial potential.

Role of anti-diabetic drugs as therapeutic agents in Alzheimer's disease

Recent data have suggested a strong possible link between Type 2 Diabetes Mellitus and Alzheimers disease (AD), although exact mechanisms linking the two are still a matter of research and debate. Interestingly, both are diseases with high incidence and prevalence in later years of life. The link appears so strong that some scientists use Alzheimers and Type 3 Diabetes interchangeably. In depth study of recent data suggests that the anti diabetic drugs not only have possible role in treatment of Alzheimers but may also arrest the declining cognitive functions associated with it. The present review gives an insight into the possible links, existing therapeutics and clinical trials of anti diabetic drugs in patients suffering from AD primarily or as co-morbidity. It may be concluded that the possible beneficial effects and usefulness of the current anti diabetic drugs in AD cannot be neglected and further research is required to achieve positive results. Currently, several drug trials are in progress to give conclusive evidence based data.

Multiple Targets for the Management of Alzheimer’s Disease

AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior. In sight of this, the proteins amyloid-beta, BACE-1, RAGE and AChE are being aimed for the treatment of AD successfully. Currently, there are several medicines for the treatment of AD under survey like Galangin, Cymserine, Tolserine, Bisnorcymserine and Huperzine A. The article emphasizes clinical and neurobiological aspects of AD. The purpose of this review article is to provide a brief introduction of AD along with the related concept of beta-secretase, beta amyloid and neurotransmitter in the progression of disease. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and neurotransmitter in the AD.

Forxiga (dapagliflozin): Plausible role in the treatment of diabetes‐associated neurological disorders

Numerous clinical and epidemiological studies have provided direct evidence to strengthen the link between type 2 diabetes (T2D) and Alzheimers disease (AD). The possibility that T2D patients might be at increased risk in developing AD has serious societal implications. Sodium glucose co‐transporter 2 (SGLT2) is one of the best targets in the treatment of diabetes, whereas acetylcholinesterase (AChE) has long been regarded as a therapeutic target for AD. This study explores the molecular interactions between AChE and SGLT2 with a new US Food and Drug Administration approved antidiabetic drug Forxiga (dapagliflozin) to explore a possible link between the treatments of AD and diabetes. Docking study was performed using “Autodock4.2.” Hydrophobic and cation–π interactions play an important role in the correct positioning of dapagliflozin within the catalytic site (CAS) of SGLT2 and AChE enzymes to permit docking. Free energy of binding (ΔG) of “dapagliflozin–SGLT2” and “dapagliflozin–CAS domain of AChE” interactions was found to be –6.25 and –6.28 kcal/mol, respectively. Hence, dapagliflozin might act as a potent dual inhibitor of SGLT2 and AChE. The results described herein may form the basis of future dual therapy against diabetes‐associated neurological disorders.

Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens

Multidrug‐resistance due to “β lactamases having the expanded spectrum” (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX‐M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug‐resistance in ESBL producing strains. Here, two CTX‐M‐15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of “cefotaxime loaded gold‐nanoparticles.” Bromelain was used for both reduction and capping in the process of synthesis of gold‐nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1‐Ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV‐Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth‐dilution method for the estimation of the antibacterial‐activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802–2808, 2017.

Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.

Compounds isolated from Ageratum houstonianum inhibit the activity of matrix metalloproteinases (MMP-2 and MMP-9): An oncoinformatics study

Background: In osteosarcoma tissue, both MMP-2 and MMP-9 are over expressed compared to their expression in non-affected stromal tissue. Hence, gelatinases are attractive targets for anti-osteosarcoma drugs. Objective: To study the inhibitory activity of compounds isolated from Ageratum houstonianum against MMP-2 and MMP-9 by in-silico approach. Material and Methods: We performed docking study using ‘Autodock 4.2’ between 1,2-benzenedicarboxylic acid-bis (2-ethylhexyl) ester; squalene; 3,5-bis (1,1-dimethylethyl) phenol; pentamethyl tetrahydro-5H-chromene; (1, 4-cyclohexylphenyl) ethanone and 6-vinyl-7-methoxy-2,2-dimethylchromene with MMP-2 and MMP-9. Results: Among all six compounds isolated from Ageratum houstonianum, (1, 4-cyclohexylphenyl) ethanone showed the maximum potential as a putative inhibitor of both MMP-2 and MMP-9 enzymes with reference to ΔG (−7.95 and −8.2 kcal/mol, respectively) and Ki (1.48 and 0.98 μM, respectively) values. Total intermolecular energy of docking for (1, 4-cyclohexylphenyl) ethanone-MMP catalytic domain-interaction was found to be −8.55 kcal/mol for MMP-2 and −9.21 kcal/mol for MMP-9. Conclusion: This study explores molecular interactions between human MMPs (MMP-2 and MMP-9) and six natural compounds. This study predicts that (1,4-cyclohexylphenyl) ethanone is a more efficient inhibitor of human MMP-2 and MMP-9 enzymes compared to the other natural compounds used in this study with reference to Ki and ΔG values.

Prevalence of CTX-M resistance marker and integrons among Escherichia coli and Klebsiella pneumoniae isolates of clinical origin.

Bacterial pathogens producing CTX‐M beta‐lactamases are emerging around the world as a source of resistance to oxyimino cephalosporins such as cefotaxime. In this study, we have investigated the prevalence of blaCTX‐M genes among clinical isolates of Escherichia coli and Klebsiella pneumoniae. Of the double‐disk synergy test‐positive E. coli (n = 94) and Kl. pneumoniae (n = 73) strains isolated during the study period, 41 (44·08%) E. coli and 32 (43·24%) Kl. pneumoniae isolates were found to be positive for blaCTX‐M genes. Twenty‐two integrons (13 for E. coli and 9 for Kl. pneumoniae) were detected whose sizes ranged from 600 bp to 1·5 kb. All these integrons were found to be of Class1 type and were invariably PCR positive for int1 and sul1 genes. Marker transfer experiments demonstrated plasmid‐mediated transfer of cefotaxime and ceftazidime resistance markers. In addition, analysis of the enterobacterial repetitive intergenic consensus (ERIC)‐PCR typing of the blaCTX‐M‐carrying isolates showed that they were genetically diverse and heterogeneous suggesting that multiple subtypes of the species were involved in infection.

An enzoinformatics study for prediction of efficacies of three novel penem antibiotics against New Delhi metallo-β-lactamase-1 bacterial enzyme

New Delhi metallo-beta-lactamase (NDM-1) is a beta-lactamase (class B carbapenemase) containing Zn2+ and other divalent cations as cofactors which possesses the ability to inactivate all beta lactams (including carbapenems) except aztreonam by catalyzing the hydrolytic cleavage of the substrate amide bond. Carbapenemases are either serine enzymes or metallo-β-lactamases (MBLs) that utilize at least one zinc ion for hydrolysis. The present study describes the molecular interaction of carbapenems (Imipenem, Meropenem, Ertapenem, Doripenem, Panipenem, Biapenem, Razupenem, Faropenem, Tebipenem and Tomopenem) with NDM-1, β-lactamase enzyme. Docking between NDM-1 and each of these carbapenems (separately) was performed using ‘Autodock4.2’.