On Infinitesimal Projective Transformations of the Tangent Bendle with the Complete Lift of a Finsler Metric

Let (M,g) be a Finsler manifold and TM0 its slit tangent bundle with the complete lift metric ~g.In this paper we prove that every infinitesimal complete lift projective transformation on (TM0,~g), is an infinitesimal affine transformation. Moreover, if (M,g) is a Landsberg manifold, then there is a one-to-one correspondence between infinitesimal complete lift projective transformations on (TM0,~g) and infinitesimal affine transformations on (M,g)

Extensive structure‐activity relationship study of albicidin’s C‐terminal dipeptidic p‐aminobenzoic acid moiety

Albicidin is a recently described natural product that strongly inhibits bacterial DNA gyrase. The pronounced activity, particularly against Gram‐negative bacteria, turns it into a promising lead structure for an antibacterial drug. Hence, structure–activity relationship studies are key for the in‐depth understanding of structural features/moieties affecting gyrase inhibition, antibacterial activity and overcoming resistance. The 27 newly synthesized albicidins give profound insights into possibilities for variations of the C‐terminus. Furthermore, in the present study, a novel derivative has been identified as overcoming resistance posed by the Klebsiella‐protease AlbD. Structural modifications include, for example, azahistidine replacing the previous instable cyanoalanine as the central amino acid, as well as a triazole amide bond isostere between building blocks D and E.BMBF, 03VP00030, Validierung einer neuen antibakteriellen Wirkstoffklasse - AlbiPharmTU Berlin, Open-Access-Mittel - 201

In vitro cytotoxic and anti-cancer effects of body wall for sea cucumber (Holothuria leucospilota)

In recent years efforts to find bioactive compounds from live organisms especially marine animals have been increased. In the present study, the anticancer and cytotoxic effects of sea cucumber body walls (Holothuria leucospilota) were investigated. For this purpose, sea cucumbers were collected from Larak Island at depths of 10 to 30 m and extraction process was done with methanol and diethyl ether solvent which then concentrated by rotary evaporator (40℃) following lyophilization with vacuum freeze dryer. XTT method was used to investigate anticancer and cytotoxic effects of body wall extracts. The results showed that the methanolic extract could prevent proliferation of human oral epidermoid carcinoma cells (KB) at concentrations of 100 and 500 μg/ml. The diethyl etheric extract also could prevent proliferation of KB at 500 μg/ml concentration. Overall result showed that sea cucumber body wall had a strong cytotoxic effect on normal cell line (Human embryonic kidney cell [HEK]) which can be used as potent cytotoxic material. However these extracts did not show significant therapeutic value against KB cells

Acetylenic Replacement of Albicidin's Methacrylamide Residue Circumvents Detrimental E/Z Photoisomerization and Preserves Antibacterial Activity

The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram‐negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, as we show here, the N‐terminal cinnamoyl moiety of albicidin is susceptible to photochemical E/Z isomerization. Moreover, the newly formed Z isomer exhibits significantly reduced antibacterial activity, which hampers the development and biological evaluation of albicidin and potent derivatives thereof. Hence, we synthesized 13 different variants of albicidin in which the vulnerable para‐coumaric acid moiety was replaced; this yielded photostable analogues. Biological activity assays revealed that diaryl alkyne analogues exhibited virtually undiminished antibacterial efficacy. This promising scaffold will therefore serve as a blueprint for the design of a potent albicidin‐based drug.DFG, 392923329, GRK 2473: Bioaktive Peptide - Innovative Aspekte zur Synthese und BiosyntheseBMBF, 03VP00030, Validierung einer neuen antibakteriellen Wirkstoffklasse - AlbiPhar