University of Tehran
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Medicinal Plants as a Source of Anti Cancer Drugs
Of the new pharmaceutical approved between 1994-2000, many of them were derived from Medicinal plants. The most important anticancer drugs from these plants are Vinblastin, Vincristine ( from Catharanthus roseus), Paclitaxel (from Taxus brevifolia), Camptothecin (from Camptotheca acuminata ) and Podophyllin (from Podophyllum peltatum). Microtubules are attractive molecular targets for anticancer therapy. There are three major binding sites on tubulin, the taxus, the vinca, and the colchicine binding site. Taxanes are examples of compounds that bind to the taxus binding site and stabilize the microtubule, whereas the majority of compounds that bind to the vinca and colchicine binding sites destabilize the microtubule and promote depolymerization by inhibition of tubulin. The first colchicines site inhibitor, colchicine, has limited therapeutic application because of its high cytotoxicity. Combretastatin A-4 (CA-4), isolated from the South African willow tree Combretum caffrom, strongly inhibits the polymerization of tubulin by binding to the colchicine site. Although CA-4 expresses high levels of in vitro activity, it does not show efficacy in vivo because of its low aqueous solubility and the isomerization of its cis-double bond into a more thermally stable, but inactive, trans isomer. As CA-4 has a simple structure, with only two aromatic rings linked by a double bond in the cis configuration, some 4,5- diaryl-imidazole or thiazole-2- thione analogues were synthesized and their cytotoxic activities in vitro against four different cell lines (HT-29, MCF-7, NIH-3T3, AGS) were evaluated. Flow cytometry analysis and microtubule polymerization assay confirmed that cytotoxic activities of this compound were related to inhibitory effect against microtubules polymerization. Furthermore, docking studies were performed to evaluate the binding mode of the active compound at the colchicine binding site of tubulin proteins.
Application of Natural Compounds in Biomimetic Reactions
Natural products are compounds that are produced by a living organism found in nature. Plants and microorganisms are the main sources of natural compounds. Semi-synthesis is a type of chemical synthesis that uses compounds from natural sources as starting materials. One of the most important pathways to find new biomimetic compounds with improved pharmacological and biological activities is semi-synthesis starting from naturally lead compounds. Here, we report the semi-synthesis of new compounds starting from ursolic acid, β-carbolines and β-lactams as natural sources by the use of multicomponent and click reactions.1,2 The products showed prominent anti-diabetic, anti-cancer and anti-bacterial activities.
Drug design based on biomimicry
The concepts of discovery and invention have been mingled in the human activities through ages. Observing an item or phenomenon and understanding it independently, for the first time, is usually considered as discovery; yet mimicking a concept that come from mother nature, is still an extension of discovery arm. However, by applying a major modification, extension, abstraction or conceptualization of nature's idea in a work, the start of a useful invention is triggered. In most cases, the two concepts are hand in hand and one comes as a prerequisite to the other. Similar rules apply in the introduction of new bioactive or drug molecules into medicine. Hence, in this way, we come up with drug discovery or drug design, in which discovery usually comes first. In this lecture, we focus on various concepts in drug development based on biomimicry and bring examples of each. One of the topics would be introducing the descriptor-base drug design and identifying the applied N-dimensional characteristics of natural molecules through building libraries of compounds.
Biological Communication Systems and Processors
In this talk I will introduce biological communication systems known as molecular communication and networking. I will also present the concept of engineering biological nano-machines to communication with biological systems at the molecular level. The fundamental mathematical models used in modeling biological systems, propagation and diffusing mechanism in cellular biological systems, biological noise and biological receiver will also be presented. Key challenges in making biological communication into practical systems will be highlighted through out our discussion and presentation.
Glycosylation optimization in Zitux (anti-CD therap eutic monoclonal antibody)
Glycosylation effect on the properties of recombinant therapeutic antibodies is well-known. It has been shown that biological activity of antibodies may be altered by variation in glycosylation pattern. Therefore, monitoring the effect of any changes in production process on glycosylation is crucial for product quality. Through process optimization for increasing anti-CD20 antibody titer in CHO-DHFR cell l line, undesirable rise in G0 was observed. Thus, addition of Galactose(G), a nucleotide sugar involved in glactosylation process, to feed media was evaluated in 10-L bioreactor. The component concentration was from 0 to 20mM. As glycan mapping analysis show G0 was rapidly decreased rapidly from 74% to less than 58% for media without of galactose and then to 20 mM. This decrease was mainly due to shift from G0 to G1 structure. The biological activity of antibody was increased from 66% to more than 100% compared to the standard. The highest change was observed when galactose concentration is increased to 20mM,in glycan mapping analysis G0 content was decreased to 58.6% compared to 74% with non-galactose feeding. The potency ratio of antibody in this case was 1 compare to reference drug. These results illustrate addition of galactose to feed medium during cell culture is an efficient approach to control of antibody galactosylation alongside mab increasing titer.
During the evolutionary period, nature has developed a diverse range of living structures, that while are adaptive to the environmental conditions, are able to perform sophisticated functions not captured by human to date. Nanbiomimetics is an emerging multi-disciplinary field of research, where natural nanoscale elements, systems and processes are studied in order to get ideas and reach solutions for resolving a range of most serious human challenges. Many advantages of nature’s solutions over human technologies appear at nanoscale. Hence, the majority of future technologies would chiefly rely on learning from nanoscale technologies already developed by the nature. Herein, I outline the fundamentals and economic prospects of mimicking nature’s technologies at nanoscale, and present sample lines of study promising development of breakthrough technologies based on nanobiomimicry.
Analyses of animal structures and bionics
One of the amazing facts about nature’s beauty is its Economy named “Parsimony”. The animal structures are product of a filtering via natural selection to keep the balance between cost and benefit leading to fitness. Using the law of constancy and consistency of characters in taxonomic studies led human to find set of naturally and economically proved and selected structures. Many mechanical designs are reproduced, or their pattern was used, based on natural structures and laws. This is considered as biological insights into mechanical design or “Bionics”. In this talk, analyses of animal structures and their use in mine engineering and industrial designs are considered. Some examples will be given on suitability of Invertebrate and vertebrate structures such as bone and body shape variations, fins, wings and other appendices actions in movement in different habitats, turbulence studies, hydro- and aerodynamics. Some natural external products of gland are artificially made and used to decrease the drag and reduce the turbulence. Here, sound detection and eco-location structures are considered. Some ultrastructural characters are selected for their use in marine construction design. Body shapes such as spherical, elliptical, and fusiform, are analyzed in some planktonic and nektonic organisms to be considered as a model in marine vessel designs.
Bionic and sustainable design
This paper is an attempt to investigate the scientific, philosophic and aesthetic issues of interdisciplinary process of bionic design, with the aim of achieving a desirable result and applying it in the process of designing industrial products, and introducing it as one of the inseparable pillars in advanced systems of engineering activities and modern technologies in order to keep the people and the environment safe as well as presenting a new and comprehensive definition for Bionic-design. Despite its appearance in industrial countries, this interdisciplinary attitude to the issue of design, have been so compatible with people’s culture and for its reciprocal relation with laws of universe and natural phenomenons, it is generalizable as a permanent and sustainable universal idea. In addition, the future prospect of bionic based on technologies and developing the “world of tomorrow” will be discussed with an outlook of this field of science. It seems that the greatest prophecy of bionic in near future is to unite the path of human societies with the sophisticated laws of nature, and inspiring from comprehensive wisdom of creator of the world in order to create ecological manufactures. Finally, it is getting closer to a sustainable technology and an idealistic product design. This approach has been organized in 3 parts: 1- Bio-morphology and the complicated relation between form, function and energy saving in nature 2- Bionic-design and its key role in global sustainable technologies 3- Conclusion and practical studies.
The peptidome refers to all of the low-molecular –weight proteins, for example endogenous peptides, in complex biological samples such as body fluids, cell lysate and tissue extract. The term ‘peptide’ is typically used for polypeptides with molecular weights of up to approximately 10 kDa. Peptidomics is defined as systematic, holistic, qualitative and quantative analysis of the endogenous peptides and small protein in biological sample at a defined time point and location. Currently, there are 20,935 proteins with known molecular weights in the UniProKB/Swiss-Prot database. Of these proteins 1,106 (~6%) belongs to proteins with molecular weight below 10 kDa. The peptidome research now has attracted increasing attention of both academia and industry due to the simplicity of sample preparation (without digestion) and recording of the current physiological states of the body as metabolic products of proteins. In this presentation, a brief description of methodology used in the peptidomics will be described. We will especially focus on the mass-spectrometry-based peptidomics and bioinformatics part analysis of the peptidome.