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The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different R f values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (n k ), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3:1 of α and β-epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1β better to 1α. The antiproliferative capacity was higher for diastereoisomer β, agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The quinoxaline core is a promising scaffold in medicinal chemistry. Multiple quinoxaline derivatives, such as the topoisomerase IIβ inhibitor XK-469 and the tissue transglutaminase 2 inhibitor GK-13, have been evaluated for their antiproliferative activity. Previous work reported that quinoxaline derivatives bearing an oxirane ring present antiproliferative properties against neuroblastoma cell lines SK-N-SH and IMR-32. Likewise, quinoxalines with an arylethynyl group displayed promising antineoplastic properties against glioblastoma and lung cancer cell lines, U87-MG and A549 respectively. Here, 40 new quinoxaline derivatives bearing an oxirane ring were synthesized using a tetrakis(dimethylamino)ethylene (TDAE) strategy and a Sonogashira cross-coupling reaction. Each reaction with TDAE furnished a pair of diastereoisomers cis and trans . These new compounds formed two series according to the substitution of position 2 on the quinoxaline core, with chlorine or phenylacetylene respectively. Each of these isomers was evaluated for antiproliferative activity against neuroblastoma cell lines SK-N-SH and IMR-32 by MTT assay. All cell viability assay results were analyzed using R programming, as well as a statistical comparison between groups of compounds. Our evaluation showed no difference in drug sensitivity between the two neuroblastoma cell lines. Moreover, trans derivatives were observed to display better activities than cis derivatives, leading us to conclude that stereochemistry plays an important role in the antiproliferative activity of these compounds. Further support for this hypothesis is provided by the lack of improvement in antineoplastic activity following the addition of the phenylacetylene moiety, probably due to steric hindrance. As a result, compounds with nitrofuran substituents from the TDAE series demonstrated the highest antiproliferative activity with IC 50 = 2.49 ± 1.33 μM and IC 50 = 3.96 ± 2.03 μM for compound 11a and IC 50 = 5.3 ± 2.12 μM and IC 50 = 7.12 ± 1.59 μM for compound 11b against SK-N-SH and IMR-32, respectively. Furthermore, an in silico study was carried out to evaluate the mechanism of action of our lead compounds and predict their pharmacokinetic properties.

South Korea is one of the largest consumers of flame-retardants worldwide. In this study, water, sediment, and biota samples were collected from a highly industrialized lake to investigate contamination, isomeric profiles, source, and the bioaccumulation potential of hexabromocyclododecanes (HBCDDs). Almost all of the sediments were severely contaminated by HBCDDs, which were some of the highest global levels compared to those found in previous studies. The highest concentrations and similar profiles to those of technical mixtures of HBCDDs were observed in creeks passing through industrial complexes, indicating on-going contamination by high consumption of HBCDDs from industrial activities. γ-HBCDD was dominant in water and sediment, whereas α-HBCDD was dominant in fish and shellfish. The diastereoisomeric profiles of HBCDDs in multiple matrices were influenced by proximity to industry and chemical properties. In-situ biota-sediment accumulation factors of α-HBCDDs were > 1 in benthic species, implying that HBCDDs are of great concern in sedimentary environments., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP and VCap). Bicalutamide and enzalutamide were used as positive controls. Compound 28 displayed significant enhancement in anticancer activity across the four PC cell lines with IC 50  = 9.09 - 31.11 µM compared to the positive controls: bicalutamide (IC 50  = 45.20 -51.61 µM) and enzalutamide (IC 50  = 11.47 - 53.04 µM). Sulfoxide derivatives of bicalutamide were prepared efficiently from the corresponding sulfides using only one equivalent of mCPBA, limiting the reaction time to 15-30 min and maintaining the temperature at 0 °C. Interestingly, three pairs of sulfoxide diastereomers were separated and NMR comparison of their diastereotopic methylene (CH 2 ) group is presented. X-ray diffraction crystal structure analysis provided relative configuration assignment at the chiral sulfur and carbon centres. Molecular modelling study of the four diastereoisomers of compound 28 is described., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A pair of new diastereoisomeric flavan, containing an additional phenylpropanoid (C 6 -C 3 ) unit in the molecule, has been isolated from the leaves of Ilex centrochinensis . Their structures were identified by extensive spectral analysis and comparison with the data of known analogues.

Heterobimetallic derivatives of a bis(carborane), [μ 7,8 -(1',3'-3'-Cl-3'-PPh 3 - closo -3',1',2'-RhC 2 B 9 H 10 )-2-( p -cymene)- closo -2,1,8-RuC 2 B 9 H 10 ] ( 1 ) and [μ 7,8 -(1',3'-3'-Cl-3'-PPh 3 - closo -3',1',2'-RhC 2 B 9 H 10 )-2-Cp- closo -2,1,8-CoC 2 B 9 H 10 ] ( 2 ) have been synthesised and characterised, including crystallographic studies. A minor co-product during the synthesis of compound 2 is the new species [8-{8'-2'-H-2',2'-(PPh 3 ) 2 - closo -2',1',8'-RhC 2 B 9 H 10 }-2-Cp- closo -2,1,8-CoC 2 B 9 H 10 ] ( 3 ), isolated as a mixture of diastereoisomers. Although, in principle, compounds 1 and 2 could also exist as two diastereoisomers, only one (the same in both cases) is formed. It is suggested that the preferred exopolyhedral ligand orientation in the rhodacarboranes in the non-observed diastereoisomers would lead to unacceptable steric crowding between the PPh 3 ligand and either the p -cymene (compound 1 ) or Cp (compound 2 ) ligand of the ruthenacarborane or cobaltacarborane, respectively., Competing Interests: The authors declare no conflict of interest.

Purpose: In the battle against cancer discovery of new and novel chemotherapeutic agent demands extreme obligation. Development of anticancer compounds with higher potency and reduced side-effects is timely and challenging., Experimental Design: A small series of fourteen diastereomeric β-lactams (seven pairs) were synthesized through multi-step process exploring [2+2] ketene-imine cycloaddition as the key step. Comparative stereochemical preferences were studied through computational docking and validated by in vitro evaluation. β-tubulin was considered as possible molecular target and in vitro anticancer evaluation was conducted against SiHa, B16F10, K562 and Chang cell lines. Caspase-3 activation assay and hematoxylin/eosin staining of the cells were also accomplished., Results: Better docking scores of the cis- over the trans-β-lactams indicated favorable β-lactam-β-tubulin interactions in cis-geometry. In vitro (IC50) evaluation confirmed better anticancer activity of the cis-diastereoisomers. Apoptosis-induced cell death was supported by caspase-3 activation study. A cis-β-lactam [(±)-Cis-3-amino-1-phenyl-4-(p-tolyl) azetidin-2-one, 6C] was found to be more active (in vitro) than the marketed natural drug colchicine against SiHa and B16F10 (six times higher potency) cell lines. Reduced toxicity (compared to colchicine) in Chang cells confirmed better site-selectivity (accordingly less side-effects) of 6C than colchicine. Aside from 6C, most of the reported molecules demonstrated good to strong in vitro anticancer activity against SiHa and B16F10 cancer cell lines., Conclusions: Stereochemical preferences of the cis-β-lactams over their trans-counterparts, toward the molecular target β-tubulin, was confirmed by docking studies and in vitro anticancer evaluation. Apoptosis was identified as the cause of cell death. The lead 6C exhibited higher potency and selectivity than the marketed drug colchicine both in silico as well as in vitro.

In order to elucidate the mechanism for diastereoisomer-specific toxicity and metabolism of hexabromocyclododecanes (HBCDs) in biota, zebrafish (Danio rerio) were exposed to different concentrations of individual HBCD diastereoisomers (α-, β- and γ-HBCD) in water for 7 and 21d. We examined the gene expression of aryl hydrocarbon receptor (AHR) and cytochrome P450 (CYP), as well as ethoxyresorufin-O-deethylase (EROD) activity in zebrafish livers. Exposure to different HBCD diastereoisomers caused different expression of AHRs in zebrafish livers. For instance, 10 and 100μgL(-1) of α- and β-HBCD up-regulated the expressions of ahr1a and ahr1b in zebrafish liver, whereas 10 and 100μgL(-)(1) of γ-HBCD down-regulated them after 7d exposure. α-HBCD showed the most significant up-regulation of ahr1a and ahr1b expression, whereas γ-HBCD showed the most significant down-regulation of their expression among three HBCD diastereoisomers. Moreover, HBCDs could affect the expression of CYP1s as well as EROD activity in a gene-specific and diastereoisomer-specific manner. α-, β- and γ-HBCD inhibited cyp1a expression but enhanced the expression of cyp1b1 and cyp1c1. α-, β- and γ-HBCD showed different degrees of effect on the same CYP1 gene in a concentration-dependent way. The different effects of HBCD diastereoisomers on these genes we examined and EROD activity not only indicate diastereoisomer-specific toxic effect, but also in turn explain diastereoisomer-specific accumulation of HBCDs in zebrafish., (Copyright © 2015. Published by Elsevier Ltd.)

S-adenosyl-l-methionine (AdoMet), an important biological cofactor, exists in two chiral forms, (S,S)- and (R,S)-, only the former of which is biologically active. Here, we have developed a chromatographic method to obtain pure (S,S)-AdoMet using a single C18 column., (Copyright © 2015 Elsevier Inc. All rights reserved.)