In Vitro and In Silico Study of Analogs of Plant Product Plastoquinone to Be Effective in Colorectal Cancer Treatment

Plants have paved the way for the attainment of molecules with a wide-range of biological activities. However, plant products occasionally show low biological activities and/or poor pharmacokinetic properties. In that case, development of their derivatives as drugs from the plant world has been actively performed. As plant products, plastoquinones (PQs) have been of high importance in anticancer drug design and discovery; we have previously evaluated and reported the potential cytotoxic effects of a series of PQ analogs. Among these analogs, PQ2, PQ3 and PQ10 were selected for National Cancer Institute (NCI) for in vitro screening of anticancer activity against a wide range of cancer cell lines. The apparent superior anticancer potency of PQ2 on the HCT-116 colorectal cancer cell line than that of PQ3 and PQ10 compared to other tested cell lines has encouraged us to perform further mechanistic studies to enlighten the mode of anti-colorectal cancer action of PQ2. For this purpose, its apoptotic effects on the HCT-116 cell line, DNA binding capacity and several crucial pharmacokinetic properties were investigated. Initially, MTT assay was conducted for PQ2 at different concentrations against HCT-116 cells. Results indicated that PQ2 exhibited significant cytotoxicity in HCT-116 cells with an IC₅₀ value of 4.97 ± 1.93 μM compared to cisplatin (IC₅₀ = 26.65 ± 7.85 μM). Moreover, apoptotic effects of PQ2 on HCT-116 cells were investigated by the annexin V/ethidium homodimer III staining method and PQ2 significantly induced apoptosis in HCT-116 cells compared to cisplatin. Based on the potent DNA cleavage capacity of PQ2, molecular docking studies were conducted in the minor groove of the double helix of DNA and PQ2 presented a key hydrogen bonding through its methoxy moiety. Overall, both in vitro and in silico studies indicated that effective, orally bioavailable drug-like PQ2 attracted attention for colorectal cancer treatment. The most important point to emerge from this study is that appropriate derivatization of a plant product leads to unique biologically active compounds.     

Tractability of convex vector optimization problems in the sense of polyhedral approximations

There are different solution concepts for convex vector optimization problems (CVOPs) and a recent one, which is motivated from a set optimization point of view, consists of finitely many efficient solutions that generate polyhedral inner and outer approximations to the Pareto frontier. A CVOP with compact feasible region is known to be bounded and there exists a solution of this sense to it. However, it is not known if it is possible to generate polyhedral inner and outer approximations to the Pareto frontier of a CVOP if the feasible region is not compact. This study shows that not all CVOPs are tractable in that sense and gives a characterization of tractable problems in terms of the well known weighted sum scalarization problems.     

A Norm Minimization-Based Convex Vector Optimization Algorithm

Journal of Optimization Theory and Applications - We propose an algorithm to generate inner and outer polyhedral approximations to the upper image of a bounded convex vector optimization problem....     

A parametric simplex algorithm for linear vector optimization problems

In this paper, a parametric simplex algorithm for solving linear vector optimization problems (LVOPs) is presented. This algorithm can be seen as a variant of the multi-objective simplex (the Evans–Steuer) algorithm (Math Program 5(1):54–72, 1973). Different from it, the proposed algorithm works in the parameter space and does not aim to find the set of all efficient solutions. Instead, it finds a solution in the sense of Löhne (Vector optimization with infimum and supremum. Springer, Berlin, 2011), that is, it finds a subset of efficient solutions that allows to generate the whole efficient frontier. In that sense, it can also be seen as a generalization of the parametric self-dual simplex algorithm, which originally is designed for solving single objective linear optimization problems, and is modified to solve two objective bounded LVOPs with the positive orthant as the ordering cone in Ruszczyński and Vanderbei (Econometrica 71(4):1287–1297, 2003). The algorithm proposed here works for any dimension, any solid pointed polyhedral ordering cone C and for bounded as well as unbounded problems. Numerical results are provided to compare the proposed algorithm with an objective space based LVOP algorithm [Benson’s algorithm in Hamel et al. (J Global Optim 59(4):811–836, 2014)], that also provides a solution in the sense of Löhne (2011), and with the Evans–Steuer algorithm (1973). The results show that for non-degenerate problems the proposed algorithm outperforms Benson’s algorithm and is on par with the Evans–Steuer algorithm. For highly degenerate problems Benson’s algorithm (Hamel et al. 2014) outperforms the simplex-type algorithms; however, the parametric simplex algorithm is for these problems computationally much more efficient than the Evans–Steuer algorithm.     

Microwave-assisted synthesis and characterization of phthalocyanines substituted with azo compound containing eugenol moiety

The new metallophthalocyanines (Co, Ni, Cu, and Zn) substituted with azo compound containing eugenol moiety are described. Firstly, azo compound (I) containing eugenol moiety was synthesized by treating eugenol with p-hydroxyaniline. Then phthalonitrile compound (1) was synthesized by microwave-assisted synthesis method. The purification of phthalonitrile compound (1) was carried out by column chromatographic separation. Intramolecular hydrogen bonding in the azo compound (I) prevent base-catalyzed nucleophilic aromatic substitution of OH group belongs eugenol. At the last step, metallophthalocyanines (1a, 1b, 1c, and 1d) were synthesized by the microwave irradiation. The microwave-assisted synthesis method reduces reaction times and enhances the yield of the reactions. All phthalocyanine compounds are soluble in DMF and DMSO. The structures were confirmed by elemental analysis, ¹H NMR, ¹³C NMR, UV/Vis, IR and Mass spectra.     

Primal and dual approximation algorithms for convex vector optimization problems

Two approximation algorithms for solving convex vector optimization problems (CVOPs) are provided. Both algorithms solve the CVOP and its geometric dual problem simultaneously. The first algorithm is an extension of Benson’s outer approximation algorithm, and the second one is a dual variant of it. Both algorithms provide an inner as well as an outer approximation of the (upper and lower) images. Only one scalar convex program has to be solved in each iteration. We allow objective and constraint functions that are not necessarily differentiable, allow solid pointed polyhedral ordering cones, and relate the approximations to an appropriate \(\epsilon \) -solution concept. Numerical examples are provided.