Mustafeez Mujtaba Babar

Design, synthesis and bioevaluation of novel umbelliferone analogues as potential mushroom tyrosinase inhibitors

Abstract A series of umbelliferone analogues were synthesized and their inhibitory effects on the DPPH and mushroom tyrosinase were evaluated. The results showed that some of the synthesized compounds exhibited significant mushroom tyrosinase inhibitory activities. Especially, 2-oxo-2-[(2-oxo-2H-chromen-7-yl)oxy]ethyl-2,4-dihydroxybenzoate (4e) bearing 2,4-dihydroxy substituted phenyl ring exhibited the most potent tyrosinase inhibitory activity with IC50 value 8.96 µM and IC50 value of kojic acid is 16.69. The inhibition mechanism analyzed by Lineweaver–Burk plots revealed that the type of inhibition of compound 4e on tyrosinase was non-competitive. The docking study against tyrosinase enzyme was also performed to determine the binding affinity of the compounds. The compounds 4c and 4e showed the highest binding affinity with active binding site of tyrosinase. The initial structure activity relationships (SARs) analysis suggested that further development of such compounds might be of interest. The statistics of our results endorses that compounds 4c and 4e may serve as a structural template for the design and development of novel tyrosinase inhibitors.

Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory.

Aluminum (Al) is a neurotoxic agent which readily crosses the blood-brain-barrier (BBB) and accumulates in the brain leading to neurodegenerative disorders, characterised by cognitive impairment. Alpha-lipoic acid (ALA) is an antioxidant and has a potential to improve cognitive functions. This study aimed to evaluate the neuroprotective effect of ALA in AlCl3-induced neurotoxicity mouse model. Effect of ALA (25mg/kg/day) was evaluated in the AlCl3-induced neurotoxicity (AlCl3 150 mg/kg/day) mouse model on learning and memory using behaviour tests and on the expression of muscarinic receptor genes (using RT-PCR), in hippocampus and amygdala. Following ALA treatment, the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) were significantly improved (p<0.05) relative to AlCl3-treated group. ALA enhanced fear memory (p<0.01) and social novelty preference (p<0.001) comparative to the AlCl3-treated group. Fear extinction memory was remarkably restored (p<0.001) in ALA-treated group demonstrated by reduced freezing response as compared to the AlCl3-treated group which showed higher freezing. In-silico analysis showed that racemic mixture of ALA has higher binding affinity for M1 and M2 compared to acetylcholine. These novel findings highlight the potential role of ALA in cognitive functions and cholinergic system enhancement thus presenting it an enviable therapeutic candidate for the treatment of neurodegenerative disorders.

Plant-Microbe Interactions: A Molecular Approach

Plants thrive in a complex environment comprising of various biotic and abiotic agents. Like all biological systems, these agents tend to interact with the plant body. Microorganisms form a major portion of the ecosystem and have been found to inoculate or infect members of all the kingdoms. Plants and microbes have developed molecular mechanisms to interact with one another and attain the maximum benefit from the interactions. This mutualistic relationship provides benefit not only to the microbes but also to the plants. Based upon this complex molecular interplay, a number of mechanisms have been studied and are currently being employed for the agricultural, environmental, and health benefits. The principles of biofertilization and bioremediation utilize the plant-microbe interactions for the survival of the two players along with contributing to the food chain and the ecosystem. Similarly, the secondary metabolites obtained from these organisms contribute to human medical and agricultural welfare. These processes are regulated by a variety of biological, physical, chemical, and environmental factors, the study of which can be helpful in exploiting better outcomes from the interaction. The advent of modern techniques has helped in deciphering the role of various molecular players of the plant-microbe interactions. Moreover, they can be employed for regulating the plant-microbe interaction for improved efficiency. The current chapter discusses the molecular mechanisms involved in the plant-microbe interactions exhibited in biofertilization, bioremediation, biocontrol, and induced systemic resistance. Afterwards, the factors affecting the molecular machinery involved in these pathways have been discussed. Toward the end, a brief introduction of the genetic manipulative techniques and their applications in the plant-microbe interactions has been presented.

Global geno-proteomic analysis reveals cross-continental sequence conservation and druggable sites among influenza virus polymerases

Influenza virus is one of the major causes of mortality and morbidity associated with respiratory diseases. The high rate of mutation in the viral proteome provides it with the ability to survive in a variety of host species. This property helps it in maintaining and developing its pathogenicity, transmission and drug resistance. Alternate drug targets, particularly the internal proteins, can potentially be exploited for addressing the resistance issues. In the current analysis, the degree of conservation of influenza virus polymerases has been studied as one of the essential elements for establishing its candidature as a potential target of antiviral therapy. We analyzed more than 130,000 nucleotide and amino acid sequences by classifying them on the basis of continental presence of host organisms. Computational analyses including genetic polymorphism study, mutation pattern determination, molecular evolution and geophylogenetic analysis were performed to establish the high degree of conservation among the sequences. These studies lead to establishing the polymerases, in particular PB1, as highly conserved proteins. Moreover, we mapped the conservation percentage on the tertiary structures of proteins to identify the conserved, druggable sites. The research study, hence, revealed that the influenza virus polymerases are highly conserved (95-99%) proteins with a very slow mutation rate. Potential drug binding sites on various polymerases have also been reported. A scheme for drug target candidate development that can be employed to rapidly mutating proteins has been presented. Moreover, the research output can help in designing new therapeutic molecules against the identified targets.

Soil Microflora – An Extensive Research

Soil is the most complicated biomaterial present on earth. It is composed of a variety of substances and provides a habitat to various organisms. Different chemical reactions take place in soil that ensures the sustainability of life. Microorganisms including bacteria, fungi, actinomyces and algae are widely distributed in soil. These natural micro flora have several advantages. They contribute to the growth and development of plants, decomposition of organic materials, nutrient cycling, soil nitrification, sustenance of pedological system and production of bioactive compounds. Soil fungi develop mutualistic associations with plants and increase their surface area for absorption. Rhizosphere of soil, the area in which micro flora is present, is rich not only in diverse micro flora but also plant roots and nutrients. Soil pollution and anthropogenic activities used for higher yield of agricultural crops negatively affect the soil micro flora. Pesticides kill micro flora and reduce soil biodiversity. The focus of this chapter is on the advantages of natural flora of soil and various factors causing their degradation. The chapter also sheds light on the changes in micro floral communities due to changes in environment. Towards the end, the future perspectives in which soil micro flora can be used for further benefit of mankind have also been discussed.

Protein sequence conservation and stable molecular evolution reveals influenza virus nucleoprotein as a universal druggable target.

The high mutation rate in influenza virus genome and appearance of drug resistance calls for a constant effort to identify alternate drug targets and develop new antiviral strategies. The internal proteins of the virus can be exploited as a potential target for therapeutic interventions. Among these, the nucleoprotein (NP) is the most abundant protein that provides structural and functional support to the viral replication machinery. The current study aims at analysis of protein sequence polymorphism patterns, degree of molecular evolution and sequence conservation as a function of potential druggability of nucleoprotein. We analyzed a universal set of amino acid sequences, (n=22,000) and, in order to identify and correlate the functionally conserved, druggable regions across different parameters, classified them on the basis of host organism, strain type and continental region of sample isolation. The results indicated that around 95% of the sequence length was conserved, with at least 7 regions conserved across the protein among various classes. Moreover, the highly variable regions, though very limited in number, were found to be positively selected indicating, thereby, the high degree of protein stability against various hosts and spatio-temporal references. Furthermore, on mapping the conserved regions on the protein, 7 drug binding pockets in the functionally important regions of the protein were revealed. The results, therefore, collectively indicate that nucleoprotein is a highly conserved and stable viral protein that can potentially be exploited for development of broadly effective antiviral strategies.

Omics-Based Bioengineering in Environmental Biotechnology

Abstract The study of genome, proteome, and metabolome is called omics. This field has enormous contributions to the advancement of green biotechnology. These newer technologies have improved the process of sequencing for environmental DNA and RNA in a cost-effective way. Assembly of genomes of organisms, for instance the soil microorganisms, can be analyzed by metagenomic and transcriptomic methods. In this chapter, various applications of omics-based bioengineering in environmental biotechnology have been discussed. These include their role in determining soil microbial ecology, controlling environmental pollution, identification of chemicals-induced toxicity and modification of geno-proteome composition of an organism.

Omics Approaches in Industrial Biotechnology and Bioprocess Engineering

Abstract The constant uncontrolled rise in the population calls for the efforts to ensure the timely availability of biopharmaceuticals to address the prophylactic and therapeutic needs of the masses. This, hence, calls for the constant upgradation and optimization of the industrial bioprocesses. Improving the output of bioprocesses to make them more cost effective and time efficient requires the incorporation and use of newer techniques. Most industrial biotechnological products involve the involvement of at least one biological organism. Therefore in order to enhance the output of these processes, an intelligent optimization of the bioprocesses has to be carried out. The advent of omics has been a tantamount to the progress in all the fields of biotechnology. A number of tools have been employed by the biotechnologists, systems biologists, and bioprocess engineers for optimizing and developing efficient industrial process for biological applications. The efficient production of quality biological products is based on the selection, optimization, and engineering of appropriate biological mechanisms. Recent advances in the field of genomics, transcriptomics, proteomics, and metabolomics have led to an overall increase in the industrial output and, hence, an improvement in the biomedical outcomes. This chapter addresses the history of the inculcation of omics technologies in the field of industrial biotechnology followed by the tools developed for improving the industrial output. The challenges faced in this sector have also been addressed.

Biotechnology and Bioengineering in Astrobiology: Towards a New Habitat for Us

Abstract Human kind is optimistic about the presence of alien civilizations in the outer space. The scientists are still working on the means to detect and make the first contact with the extraterrestrials. The current focus is on the search of nonintelligent microbial life forms. Moreover, efforts are underway to identify the optimum conditions to support life on other planets. Before the dawn of the space age, the moon was considered to be just a barren land formed by the ancient impact craters. Similarly Mars was just a distant planet and Venus was boiling cauldron of molten rock shrouded in dense and poisonous atmosphere. Significant progress has, however, been made after the recent discoveries in the field of astrobiology, astrobiotechnology, and synthetic space biology. This chapter presents the conditions that support life in the outer space. Techniques employed for the identification and detection of organic molecules, fossilized microorganisms, and minerals have also been discussed. Moreover, the potential of life outside earth with reference to the extremophile organisms has been addressed. Finally, the future role of astrobiology in finding new home for the living organisms has been discussed.

Omics Approaches in Forensic Biotechnology: Looking for Ancestry to Offence

Abstract Forensic biotechnology deals with the study and investigation of genomic information for the identification of specific signatures. The data obtained from forensic biotechnology are utilized by the legal system to make necessary interpretations about criminals. Because of its potential to identify unique genetic markers, the discipline has also been employed for the determination of parenthood or other familial characteristics. Traditionally this field relied on a few basic techniques of genetics like DNA fingerprinting. However, the recent developments in the field of genomics, transcriptomics, and proteomics have made the forensic sciences increasingly sensitive and reliable. The availability of the minutest amount of sample (like blood, hair, or other body tissues) can help in extracting the information in a timely manner that would otherwise have taken months to years to obtain. This chapter provides an introduction about the basic techniques involved in forensic technology. The developments in the field of omics sciences and how they have contributed to the field of forensic biotechnology have also been discussed.