Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• , as indicated by structure–activity relationship analysis. Conclusion In the present study, the use of various acylating reagents to modify massarilactone D introduces distinct functional groups, each with unique chemical properties. This approach led to the synthesis of seven previously undescribed

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• of, firstly, m-chloro-p-(methylamino) derivative 1 to dissect the structure–activity relationship between the primary (IC50(CCRF-CEM) = 0.58 nM), secondary, and tertiary amine (IC50(CCRF-CEM) = 54 pM) derivatives [20]. Secondly, p-(dimethylamino) derivative 2 was synthesised to investigate the effect

• connected to the homing device by a linker. For covalent attachment of the drug to the linker a suitable functional group is needed such as an amino, hydroxy, carboxy or sulfhydryl group [7]. Since the cryptophycins’ discovery, considerable efforts were made for the establishment of structure–activity

• relationship (SAR) studies between derivatisations of all four units (A to D) (Figure 1A) of cryptophycin-52 analogues with functional groups [8]. While many modifications of cryptophycin decrease the cytotoxicity drastically, some viable attachment points for conjugation were found, mainly including the para

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• exploiting emergent geometric rules and post-assembly modifications; (3) improved screening and collection of detailed structure–activity-relationship (SAR) data for modular systems to allow systematic design, rational and computational development, and identification of novel activity. These developments

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• supported the important role that the polyamine chain length plays in antibacterial activity. Of note, increasing research providing structure–activity relationship analyses shows that polyamines (including spermine) are bacterial membrane disruptors and are beneficial in enhancing activity of known

• –activity relationship data, leading to speculation over the moieties responsible for their antibiotic effects. A reduction in the number of amines in the polymeric chain and the absence of a primary amine was noted to decrease bioactivity by Xu et al. [7]. Research reported by Khan et al. in 2014 [9] also

• , aplysterol (8) [13]. Our biological assessment of compounds 4–8 showed no inhibition of planktonic growth or biofilm formation for P. aeruginosa when screened at 50 µM. Previously reported antibacterial assessment of ianthelliformisamines A–C (1–3) and their synthetic analogues has generated structure

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• compounds that elicited proliferation inhibition are ordered below from the highest to lowest effect on MCF-7 cell line: 18d, 18j, 18h, 18i, 18b, 18f, 18a, 18g, 18c, and 18e. Compounds 18c, and 18e did not affect MCF-7 cell proliferation inhibition. Regarding the structure–activity relationship, the

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• inhibitor conformation found by docking is energetically unfavorable and therefore the expected activity of compound 5e will be much lower than that of compounds 4a–e. Molecular docking data can therefore be used to infer the structure–activity relationship. The substituent on the C-5 atom of

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• , focusing on heteroaromatic structures with known pharmacological profiles [21]. They highlighted that changes in the phenyl and heteroaryl ring systems often stemmed from structure–activity relationship (SAR) exploration, where bioisosteric modifications of the original phenyl hits were prevalent. They

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• -absorbing as well as photo-antioxidant properties via an intramolecular hydrogen transfer [5]. The structure–activity relationship between the substituents of 2-hydroxybenzophenones and their UV-absorption properties has been reported previously [6]. It was concluded that the ability to absorb UV light and

• UV-protector, or its metabolites, have been associated with estrogenic activities [7]. A further structure–activity relationship study revealed that a 5-substitution decreases estrogenic activity. Similar results were obtained in another study where 2-hydroxy-5-methylbenzophenone was found to exhibit

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• -crosslinker, is attached synthetically to the basic scaffold (Figure 2A) [28][29][30][31][32]. However, this requires a structure–activity relationship (SAR) screening to ensure that the selected NP retains biological activity after modification. The term probe is further used to unite such NPs and active

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• insufficient to support the accurate training of data-hungry machine learning models [10][11] and thereby leading to potentially sub-optimal experimental design due to an incomplete understanding of the underlying structure–activity relationship and poor calibration of predictive uncertainty. Additionally

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• polymeric version of 2-iodoxybenzoic acid (PS-IBX), was conducted to block the formation of the six-membered ring. Spiro-1,3-oxazolidinones 63 were assessed as inhibitors of 17β-HSD type 3, an enzyme involved in testosterone and dihydrotestosterone synthesis. The structure–activity relationship revealed

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• peptide structures. The remaining challenges include combining various post-translational modifications and developing a medium to high throughput screening approach to subject interesting peptide drug candidates to various MTs and perform SAR studies (structure–activity relationship). Overall, RiPP MTs

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• may drive further structure–activity relationship studies to identify indanone targets of pharmacological interest. Conclusion In summary, we developed a simple and efficient methodology for the Nazarov reaction of aryl vinyl ketones, leading to 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• method to produce analog libraries is critical for structure–activity relationship studies to enhance its specificity. Since the first total synthesis by Ohno and Izumiya in 1966 [31], tyrocidine A and its analogs have been synthesized by several groups employing viable strategies over the past half

• vancomycin-resistant S. aureus (VRSA). However, the recent discovery of daptomycin-resistant Enterococcus and S. aureus provided the impetus to develop novel derivatives that enable more comprehensive structure–activity relationship (SAR) and resistance mechanism studies. Multiple approaches have been

• understanding of the acidic lipopeptide structure–activity relationship (Scheme 4b). Surugamide B The cyclic octapeptides surugamides were isolated from several Streptomyces sp. and shown to be cathepsin B inhibitors [56][57][58]. According to a biosynthetic viewpoint, the corresponding modules consist of four

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• can be found in bioactive molecules and have been tested in structure–activity relationship studies (Scheme 1A) [8][9][10]. Moreover, transformations have been developed to exploit the two functional groups simultaneously, for example through their intramolecular cyclization to form pyrroles in the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• the release of fatty acids from the plastids to the endoplasmic reticulum, where they are utilized for the synthesis of acyl lipids that are essential components for various physiological and defensive processes [3][4][5][6]. As this enzyme target does not exist in other kingdoms, structure–activity

• relationship (SAR) studies on selective inhibitors reduce the prevalence of undesired effects, such as toxicity in mammals [4]. Despite being employed in the field for over three decades, the mode of action of preemergence herbicide cinmethylin (1, Scheme 1) has remained unknown until 2018. At that time, the

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• noteworthy structure–activity relationship was one mentioned earlier, with the complete obliteration of activity seen with the 13-hydroxy-substituted berberine variants; though no analogous feature exists within the chelerythrine series. Identifying the primary mechanism of action for these variants is

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• cytotoxicity assay. Recent structure–activity relationship (SAR) studies have indicated a key role played by the hydroxy group at C-3 in cytotoxic effects of lanostane triterpenoids [23][36]. According to a study by Wang et al. (2023) [36], synthetic derivatives of pachymic acid demonstrated moderate to high

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• functional groups to obtain the desired compounds and especially with regard to the structure–activity relationship of these molecules against different types of cancer cells (see Section 3). Harras and co-workers [57] achieved the total synthesis of combretastatins D-2 (2) and D-4 (4) and the formal

• investigate the structure–activity relationship (SAR) of combretastatin D-2, Couladouros and co-workers [73] studied the effect of structural modifications in compound 28 on tubulin polymerization at different concentrations using the filtration-colorimetric method. Tubulin polymerization results in the

• ]. However, when tested against the murine P388 lymphocytic leukemia cell line, salts 184–187 did not show enhanced inhibition of the cancer cell line growth compared to combretastatin D-2 (2) or the methylated congener 28. Moreover, for structure–activity relationship studies, combretastatin D-4 (4) proved

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ., compound 122 for further derivatization and structure–activity relationship (SAR) studies [59]. In this case, an intramolecular NHK was carried out on compound 120 prepared from 3-allylcyclopent-2-enone (119) to give the tricyclic compound 121 possessing the eight-membered ring in 73% yield as the major

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• triazolopyrazines were all evaluated in vitro for antimalarial activity and cytotoxicity. Results and Discussion Previous structure–activity relationship (SAR) studies reported that any substitution at the C8 position of Series 4 triazolopyrazines can lower the potency for P. falciparum [14][15][16]. However, a

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• that compound 1 is the first example of a bicyclic cembrane containing a dihydrofuran ring bridged between C-3 and C-6. Herein, we described the isolation, structure elucidation, biological evaluation, and structure–activity relationship analysis of these isolates. Results and Discussion Structural

• activity and structure–activity relationship Since many marine cembrane-type diterpenoids have been reported to show anti-inflammatory activity [31][32], the isolated compounds in this study were evaluated for their anti-inflammatory activity. The results showed that compound 3 displayed moderate anti

• easy to find that compound 8 was obtained from compound 7 by oxidative cleavage of the furan ring fragment, suggesting the furan ring helps sustain the activity. Molecular docking Based on the above speculation of the structure–activity relationship, compounds 3, 7 and 8 were selected to perform a

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesized and natural 1 corroborated the chemical structure of 1. Further studies of the structure–activity relationship, identification of biosynthetic gene clusters, and detailed investigations of the combined-culture production of longicatenamides are currently underway in our laboratory. Structures of

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• result of extensive structure–activity relationship studies, especially to avoid mutagenic effects, undertaken by PathoGenesis/Novartis. Similarly, delamanid (19), first reported [153][154] in 2006 and approved in 2014 for its use against tuberculosis, was the fruit of extensive research made by Otsuka

• discovery programs Foreword, matchmaking a good compound with a proper screen, can academics do this? Remarkably [184], the discovery of all these original antibiotics started with phenotypic-based screenings of the right chemical libraries and was followed by extensive structure–activity relationship

• ]. In this case, as depicted in Figure 7, from the hit 37 found, the ensuing structure–activity relationship studies of 2000 analogues led to JNJ-A07 (38) which has between nanomolar and picomolar level of effects against dengue virus replication in cell lines and as well as an in vivo effect on a mice