Pharmacophore Modeling and Docking Studies on Some Nonpeptide-Based Caspase-3 Inhibitors

Neurodegenerative disorders are major consequences of excessive apoptosis caused by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has become a validated therapeutic approach for neurodegenerative disorders. We performed pharmacophore modeling on some synthetic derivatives of caspase-3 inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in the common pharmacophore hypothesis AAHRR.6 which might be responsible for the biological activity: two aromatic rings (R) mainly in the quinoline nucleus, one hydrophobic (H) group (CH3), and two acceptor (A) groups (–C=O). After identifying a valid hypothesis, we also developed an atom-based 3D-QSAR model applying the PLS algorithm. The developed model was statistically robust (q2=0.53; pred_r2=0.80). Additionally, we have performed molecular docking studies, cross-validated our results, and gained a deeper insight into its molecular recognition process. Our developed model may serve as a query tool for future virtual screening and drug designing for this particular target

Chemometrics: A new scenario in herbal drug standardization

Chromatography and spectroscopy techniques are the most commonly used methods in standardization of herbal medicines but the herbal system is not easy to analyze because of their complexity of chemical composition. Many cutting-edge analytical technologies have been introduced to evaluate the quality of medicinal plants and significant amount of measurement data has been produced. Chemometric techniques provide a good opportunity for mining more useful chemical information from the original data. Then, the application of chemometrics in the field of medicinal plants is spontaneous and necessary. Comprehensive methods and hyphenated techniques associated with chemometrics used for extracting useful information and supplying various methods of data processing are now more and more widely used in medicinal plants, among which chemometrics resolution methods and principal component analysis (PCA) are most commonly used techniques. This review focuses on the recent various important analytical techniques, important chemometrics tools and interpretation of results by PCA, and applications of chemometrics in quality evaluation of medicinal plants in the authenticity, efficacy and consistency. Key words: Chemometrics, HELP, Herbal drugs, PCA, OP

Optimal control of a CSTR process

Designing an effective criterion and learning algorithm for find the best structure is a major problem in the control design process. In this paper, the fuzzy optimal control methodology is applied to the design of the feedback loops of an Exothermic Continuous Stirred Tank Reactor system. The objective of design process is to find an optimal structure/gains of the Robust and Optimal Takagi Sugeno Fuzzy Controller (ROFLC). The control signal thus obtained will minimize a performance index, which is a function of the tracking/regulating errors, the quantity of the energy of the control signal applied to the system, and the number of fuzzy rules. The genetic learning is proposed for constructing the ROFLC. The chromosome genes are arranged into two parts, the binary-coded part contains the control genes and the real-coded part contains the genes parameters representing the fuzzy knowledge base. The effectiveness of this chromosome formulation enables the fuzzy sets and rules to be optimally reduced. The performances of the ROFLC are compared to these found by the traditional PD controller with Genetic Optimization (PD_GO). Simulations demonstrate that the proposed ROFLC and PD_GO has successfully met the design specifications