Microtermolides A and B from Termite-Associated Streptomyces sp. and Structural Revision of Vinylamycin

Microtermolides A (1) and B (2) were isolated from a Streptomyces sp. strain associated with fungus-growing termites. The structures of 1 and 2 were determined by 1D- and 2D-NMR spectroscopy and high-resolution mass spectrometry. Structural elucidation of 1 led to the re-examination of the structure originally proposed for vinylamycin (3). Based on a comparison of predicted and experimental $^1$H and $^{13}$C NMR chemical shifts, we propose that vinylamycin’s structure be revised from 3 to 4

Studies on the Himalayan yew <i>Taxus wallichiana: </i>Part IX — The chemical constituents of the seeds of <i>Taxus wallichiana</i>

225-227The systematic investigation on the seeds of Taxus wallichialla has resulted in the isolation of three non-taxoid constituents, ursolic acid 1, the cyanogenic glycoside amygdalin 2 and β-sitosterol glucoside 3. It is a very important finding that the seeds of the Himalayan yew did not contain any taxoids in contrast to the presence of taxoids in the seeds of other species of Taxus and amygdalin is the major constituent of the seeds. The detailed NMR data of amygdalin are also provided

Indole-Based Fibrates as Potential Hypolipidemic and Antiobesity Agents

Hypolipidemic and antiobesity effects of the newly synthesized indole-based fibrates were evaluated in Triton WR-1339 and high fat diet (HFD)-induced hyperlipidemic rats. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton model), in which compounds <b>3f</b> and <b>3l</b> showed significant antidyslipidemic activity. Furthermore, these compounds <b>3f</b> and <b>3l</b> were found to induce significant weight loss in the visceral fat mass of HFD-fed hyperlipidemic rats without affecting the normal feeding behavior. Histological examination of the liver of rats supplemented with <b>3f</b> and <b>3l</b> revealed a significant decrease in steatosis when compared to the effect of the standard drug fenofibrate. Additional effects such as an increase in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catabolism of I¹³¹-low density lipoproteins (LDL) confirm and reinforce the efficacy of both of these compounds as a new class of dual-acting hypolipidemic and antiobesity agents

Development of Leishmania donovani stably expressing DsRed for flow cytometry-based drug screening using chalcone thiazolyl-hydrazone as a new antileishmanial target

Green fluorescent protein produces significant fluorescence and is extremely stable, however its excitation maximum is close to the ultraviolet range and thus can damage living cells. Hence, Leishmania donovani stably expressing DsRed were developed and their suitability for flow cytometry-based antileishmanial screening was assessed by evaluating the efficacies of standard drugs as well as newly synthesised chalcone thiazolyl-hydrazone compounds. The DsRed gene was successfully integrated at the 18S rRNA locus of L. donovani and transfectants (LdDsRed) were selected using hygromycin B. Enhanced expression of DsRed and a high level of infectivity to J774A.1 macrophages were achieved, which was confirmed by fluorescence microscopy and flow cytometry. Furthermore, these LdDsRed transfectants were utilised for development of an in vitro screening assay using the standard antileishmanial drugs miltefosine, amphotericin B, pentamidine and paromomycin. The response of transfectants to standard drugs correlated well with previous reports. Subsequently, the suitability of this system was further assessed by screening a series of 18 newly synthesised chalcone thiazolyl-hydrazone compounds in vitro for their antileishmanial activity, wherein 8 compounds showed moderate antileishmanial activity. The most active compound 5g, with ca. 73% splenic parasite reduction, exerted its activity via generating nitric oxide and reactive oxygen species and inducing apoptosis in LdDsRed-infected macrophages. Thus, these observations established the applicability of LdDsRed transfectants for flow cytometry-based antileishmanial screening. Further efforts aimed at establishing a high-throughput screening assay and determining the in vivo screening of potential antileishmanial leads are required

Novel Chalcone–Thiazole Hybrids as Potent Inhibitors of Drug Resistant <i>Staphylococcus aureus</i>

A series of novel hybrids possessing chalcone and thiazole moieties were synthesized and evaluated for their antibacterial activities. In general this class of hybrids exhibited potency against <i>Staphylococcus aureus</i>, and in particular, compound <b>27</b> exhibited potent inhibitory activity with respect to other synthesized hybrids. Furthermore, the hemolytic and toxicity data demonstrated that the compound <b>27</b> was nonhemolytic and nontoxic to mammalian cells. The <i>in vivo</i> studies utilizing a <i>S. aureus</i> septicemia model demonstrated that compound <b>27</b> was as potent as vancomycin. The results of antibacterial activities underscore the potential of this scaffold that can be utilized for developing a new class of novel antibiotics