Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus

The benzo[b]thiophene nucleus and the acylhydrazone functional group were combined to prepare three new series of compounds for screening against Staphylococcus aureus. The reaction of substituted benzo[b]thiophene-2-carboxylic hydrazide and various aromatic or heteroaromatic aldehydes led to a collection of 26 final products with extensive structural diversification on the aromatic ring and on position 6 of the benzo[b]thiophene nucleus. The screening lead to the identification of eight hits, including (E)-6-chloro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.b), a non-cytotoxic derivative showing a minimal inhibitory concentration of 4 µg/mL on three S. aureus strains, among which were a reference classical strain and two clinically isolated strains resistant to methicillin and daptomycin, respectively.

The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity

Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing and matching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the Acore domains, yet domain interfaces and the flexible Asub domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches.

STRATEGIC MANAGEMENT IN ECONOMIC SYSTEMS OF TRANSITIVE COUNTRIES

The evolution and structural aspects of strategic management are considered. The role of strategic management in managing changes in the economy of transition countries, where economic structures have been disintegrated, is revealed. The most significant relationships between strategic forecasting and strategic planning, as well as between strategic management and specific types of management are analyzed. The general algorithm of strategic planning and strategic management in economic systems, and also terminology in the researched field of knowledge is defined. The problems of strategic management arising from the narrowing of the structure of the economy of transition countries are studied. The relationship between the functional diversity of strategic management and structural diversification of the national economy is revealed. Emphasis is placed on new directions of economic science development that will influence the theory of strategic management. The main types of strategy of economic systems operating in the conditions of open economy and globalization are substantiated. The necessity of applying the principles of hierarchy and iterative approach in the process of strategic management is proved. Classified typical features of strategic management that distinguish it from current management by the nature of the impact. The author's model of strategic planning on the example of optimization of the innovative program of the enterprise by means of methods of linear programming is given. Substantiated recommendations on strategic priorities and institutional mechanisms that will help increase the effectiveness of strategic management based on the structural diversification of the economy of Ukraine, its regions and enterprises. Among the strategic priorities, the main attention is paid to the following priorities: modernization of the real sector of the economy; state support of enterprises that reinvest profits in innovation; equalization of regional disparities on the basis of strategy of specialization and interregional cooperation; formation of national and transnational clusters; involvement of Ukraine in the European policy of specialization and digitalization; implementation of international communication projects and long-term logistics strategy.

Recent progress in environmental applications of metal-organic frameworks

Nanomaterials have aroused the interest of many researchers and become a research hotspot in recent years and metal-organic frameworks (MOFs) included in that are a class of new organic-inorganic hybrid porous materials formed through the self-assembly of organic ligands and inorganic metal ions. MOFs have been attracting increasing attention due to their structural diversification, large specific surface area, high porosity, inerratic pore space framework. These characteristics play their advantages in different fields and make some excellent achievements. This article summarizes the research progress of metal-organic framework in the field of environment especially the remarkable achievements in adsorption and provides a clear help for understanding the research progress and prospects for future research.

From Target-Oriented to Motif-Oriented: A Case Study on Nannocystin Total Synthesis

Natural product total synthesis is in essence target-oriented in that a set of organic transformations are orchestrated into a workable process, leading ultimately to the target molecule with a predefined architecture. For a bioactive lead, proof of synthetic viability is merely the beginning. Ensuing effort repurposes the initial synthesis for structural diversification in order to probe structure-activity relationship (SAR). Yet accessibility is not equal to flexibility; moving from convergency to divergency, it is not always feasible to explore the chemical space around a particular substructure of interest simply by tweaking an established route. In this situation, the motif-oriented strategy becomes a superior choice, which gives priority to synthetic flexibility at the concerned site such that a route is adopted only if it is capable of implementing diversification therein. This strategy was recently devised by Fürstner et al., enabling them to achieve total synthesis of both natural and non-natural nannocystins varied at an otherwise challenging position. The present review examines seven distinctive nannocystin total syntheses reported thus far and showcases the merits of conventional (target-oriented) as well as motif-oriented strategies, concluding that these two approaches complement each other and are both indispensable for natural product based drug discovery.