Synthesis and Cytotoxicity Evaluation of Spirocyclic Bromotyrosine Clavatadine C Analogs

Marine-originated spirocyclic bromotyrosines are considered as promising scaffolds for new anticancer drugs. In a continuation of our research to develop potent and more selective anticancer compounds, we synthesized a library of 32 spirocyclic clavatadine analogs by replacing the agmatine, i.e., 4-(aminobutyl)guanidine, side chain with different substituents. These compounds were tested for cytotoxicity against skin cancer using the human melanoma cell line (A-375) and normal human skin fibroblast cell line (Hs27). The highest cytotoxicity against the A-375 cell line was observed for dichloro compound 18 (CC₅₀ 0.4 ± 0.3 µM, selectivity index (SI) 2). The variation of selectivity ranged from SI 0.4 to reach 2.4 for the pyridin-2-yl derivative 29 and hydrazide analog of 2-picoline 37. The structure–activity relationships of the compounds in respect to cytotoxicity and selectivity toward cancer cell lines are discussed.     

A linear programming algorithm and software for forest-level planning problems including factories

Combining stand simulation and forest-level optimization is an efficient way to study harvest scenarios of a forest area. A simulator first generates for each treatment unit a number of treatment schedules. Linear programming (LP) can then be used to study how stand-level schedules can be combined at the forest level with respect to alternative goals and constraints. The special structure of the obtained LP problems can be utilized using the generalized upper-bound technique which takes care of the so-called area constraints. JLP software was based on this technique. Later J software was developed to replace JLP. Now J is developed to deal with factory problems where the transportations costs and capacities of factories are included in the problem definition. The generalized upper-bound technique was modified to handle transportation constraints which tell that each timber unit produced is transported to some of the factories. The number of these constraints is very large. This paper describes the basic features of the algorithm and its implementation in the J software.