Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• -spectrum effects, including antibiofilm and antifungal properties [24]. Notably, these compounds also disrupt microbial membranes via lytic or non-lytic mechanisms (e.g., pore formation, lipid extraction, or inhibition of essential enzymes like ATP synthases) [25][26][27][28]. The antimicrobial activity

• antimicrobial properties of surfactants are promising, offering novel possibilities for anti-infective agents [24]. Surfactants act mainly by the destabilization of the cell membrane, which compromises the selectivity and homeostasis of the microorganism; they also act with the inhibition of essential enzymatic

• synthesis), inhibiting their activity through steric hindrance and hydrogen bonding [60][97]. The arginine-derived surfactant lauroyl-arginine ethyl ester shows notable DNA gyrase inhibition at 32 μg/mL (IC50 = 18.7 μM), effectively halting bacterial replication [97]. Tryptophan-based analogs exhibit strong

Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with duplex and abasic site-containing DNA

• Laurin Beckmann,
• Jason Lennard Kunze,
• Hannah Karola Strunk,
• Maurice Michel and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 1057–1066, doi:10.3762/bjoc.22.84

• released from a Boc-protected precursor and that the corresponding coralyne–alkoxyamine conjugate can operate as a ligand for AP-DNA and as inhibitor of enzymatic repair of abasic sites. Keywords: APE1 inhibition; DNA binders; N-hetarenes; papaverine; protoberberines; Introduction DNA is a main target in

• the development of antitumor agents, because the inhibition or restriction of the essential functions of DNA has a strong influence on cell viability [1]. Therefore, the search for new compounds that selectively bind to DNA and thus significantly influence its biological activity is still an

• with a more efficient preliminary DNA binding of the ligand before covalent connection. Herein, we report on our general attempts to synthesize coralyne derivatives with additional substituents in position 13 as well as exemplary studies of their ability for DNA binding and enzyme inhibition. Results

Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• chronic and neuropathic pain, whereas its inhibition (A1 antagonism) leads to increased alertness and modulation of renal blood flow [63][65]. The predicted binding affinities of the 7a–ay derivatives, evaluated in both possible enantiomeric forms (R and S), together with those of the co-crystallized

Semisynthesis, characterisation, and antibacterial evaluation of a novel lecanoric acid-derived amide library

• Ethan D. Abbott,
• Sasha Hayes,
• Jonathan M. White,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 1023–1032, doi:10.3762/bjoc.22.81

• evaluated for antibacterial activity against the human pathogen Pseudomonas aeruginosa using a biofilm inhibition assay. Of the new semisynthetics, amide analogue 12 showed the greatest planktonic cell growth inhibition (13% at 50 µM), whilst amide analogue 11 was the most active at inhibiting the formation

• biofilm inhibition assay that used the Gram-negative pathogen, Pseudomonas aeruginosa [27]. P. aeruginosa is an opportunistic and drug resistant nosocomial pathogen, which is responsible for an increasing number of fatal infections in critically-ill individuals [28]. The pathogen’s increasing resistance

• formation. Overall, no significant activity was exhibited by any of the compounds at 50 µM. The natural products orcinol (3) and orsellinic acid (4), along with the new semisynthetic amide 11, were shown to be the three most active compounds in the biofilm assay with inhibition values of 25%, 11%, and 21

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• an inhibition of the catalyst’s oxidative addition to the C–I bond. Notably, the substrates containing electron-withdrawing groups, such as cyano or nitro groups, resulted in low yields, even after longer reaction times (Table 3, entries 7 and 8). These results were attributed to homo-coupling of 1

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• -luciferase reporter gene assay. As demonstrated in Figure 1, among the designed dual-target modulators, compounds Z8, Z11, Z17, and Z30 exhibited the most potent effects at a concentration of 10 μM. ASK1 Inhibition The inhibitory activity against ASK1 was evaluated using the ADP-Glo™ kinase assay. A screen

• of the designed dual-target modulators identified 17 compounds that inhibited ASK1 (Figure 2). Among the compounds examined, Z8 demonstrated the greatest potency, exhibiting an inhibition rate of 84.59% at a concentration of 10 μM. Lipid-modifying activity In light of the prevalence of the reduction

• -luciferase reporter assay in CHO cells cultured for 24 hours following addition of GW4064 and test compounds. Compared to the control group, **p < 0.01 and ns indicate no significant difference, with control; DMSO serving as the control group. ASK1 inhibition of all compounds. Results of the ADP-Glo™ kinase

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• inhibition of root growth of Arabidopsis thaliana. The RLIT data is compared with those previously reported for two series of compounds having the same substitution pattern at C-22 but different structure in ring A. This comparison revealed that a 2α,3α-dihydroxy configuration is more active than a 3

• inhibition of root and hypocotyl elongation in Arabidopsis thaliana seedlings, among other bioassays. The results show that for the same BRs, the measured effects vary with the bioassay and concentration. For example, in the RLIT the growing effect increases with increasing concentration, whereas on root

• matter of current interest. For example, derivatives of teasterone (3), compounds 4–11, and castasterone, compounds 12–14, with benzoyl function at C-22 (Figure 2) have been synthesized, and their bioactivities have been evaluated by BSIB, RLIT, and inhibition of root and hypocotyl elongation in A

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• (MIC = 25 µM), and Malassezia furfur (MIC = 12.5 µM) [20]; antioxidant activity with the inhibition of CuSO4-induced peroxidation of low-density lipoprotein in a concentration-dependent manner from 0.1−10 µM [21], and anti-invasiveness activity on HT115 human colon cancer cells at a concentration

• transwell invasion assay (Figure 7), (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol (6) was selected for further study. The U251MG cells were treated with different concentrations of 6 (0.03, 0.1, 0.3, and 1 µM) over 5 h and assayed for inhibition of invasion. The IC50 for compound 6 was calculated as 0.26 µM

• (Figure 7B). The KNS42 cells were treated with different concentrations of (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol (6, 0.03, 0.1, 0.3, and 1 µM) for 5 h and assayed for inhibition of invasion (Figure 8A). The compound inhibited invasion at 0.3 and 1 µM by up to 30%, and the IC50 for compound 6 was

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• including cytotoxicity and melanogenesis inhibition [28][29][30][31][32]. Furthermore, compound 2 is the active principle of a renal antispasmodic product Proximol®, derived from desert weed Cymbopogon proximus which is used as the folk medicine in Egypt [29]. One formal total synthesis of both compounds 2

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• HDACs are closely related to the occurrence of many types of cancers [74][75][76]. Abnormal expression of HDACs will significantly affect the occurrence, development, and migration of cancer [77][78][79][80]. Although an inhibition of HDACs by inhibitors can induce apoptosis and restrain cancer

• ][99]. The reasons for the failure are rarely discussed but one of the factors is believed to be due to the inhibition of several p38MAPK proteins [98]. Therefore, how to specifically target p38MAPK family members has become a vital issue in the development of drugs. In this regard, PROTAC again shows

• : Serum-glucocorticoid-induced protein kinase (SGK) plays a key role in mediating resistance to phosphoinositide 3-kinase (PI3K)/Akt inhibition in breast cancer cells [132]. It has been reported that different ATP competitive inhibitors have similar affinity for all SGK isoforms [133][134]. Due to the

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• adjacent to the ATP-binding site of CK2α [5][6]. Fragment-based ligand discovery subsequently enabled the development of CAM4066, a selective inhibitor that simultaneously engages the αD and ATP sites. CAM4066 validated the αD region as a tractable and selective binding pocket for CK2 kinase inhibition

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• SOS response is a global response to DNA damage which can occur due to several reasons, including, but not limited to, inhibition of enzymes such as DNA gyrase, DNA polymerase or topoisomerases I and IV. We conducted studies of inhibitory activity of samples 3h, 3g and 4b against the above-mentioned

• polymerase I extend them to form a complete product of 142 bases. If the DNA polymerase is inhibited by an antibiotic, the synthesis of the full-length product will be impaired, and the complete product will not be generated. Subsequently, inhibition of DNA polymerase can disrupt DNA replication, leading to

• inhibit DNA polymerase I activity. Next, we examined the potential inhibition of DNA cleavage mediated by DNA gyrase or DNA topoisomerase IV (Topo IV). In this test (Figure 4A), supercoiled DNA is present within the system. Topo IV catalyzes an ATP-dependent cleavage of both DNA strands, followed by the

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• confirm that the conjugation of CI-994 to the nanogold particle did not significantly affect HDAC inhibition. The HDAC1-LSD1-CoREST complex, incorporating a FLAG tag in CoREST, was expressed and purified from HEK293F cells as previously reported [10]. Fluorescent deacetylase assays were carried out using

• -complete inhibition of the HDAC activity in the CoREST complex, even at 0.54 μM. Surprisingly, Au–NH2 was found to reduce the HDAC activity of the CoREST complex by nearly 50%. One plausible explanation for this effect is a direct interaction between the gold nanoparticles and solvent-accessible cysteine

• complex and diminishing its deacetylase function. However, the maximal HDAC inhibition by Au–NH2 was considerably less compared to Au–(CI-994) and CI-994, suggesting Au–(CI-994), is inhibiting HDAC enzymatic activity by direct competition for the HDAC active site. We next determined the IC50 of Au–(CI-994

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• demands of the proliferative state creates an opportunity to selectively target cancer cells [1][7]. Chemical inhibition of GLS has emerged as an attractive anticancer strategy, and several classes of GLS inhibitors have been discovered [1][2]. DON is a diazo-containing electrophilic glutamine analog that

• glutaminase inhibition on several cancer cell lines (Figure 1) [15][16]. The anticancer effects of compound 968 have been tested in combination with other drugs such as paclitaxel [17], erlotinib [18], apigenin [19], metformin [20], and inhibitors of tissue transglutaminase [21]. Compound 968 was recently

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• enhancing lysosomal membrane permeability and aqueous solubility [42]. Interestingly, for the first time, N-(n-octyl) chain substitution has been shown to demonstrate remarkable anticancer activity, particularly through tyrosine kinase inhibition, without significant DNA intercalation [43]. Among these

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• carcinoma cells), and T98G (Human glioblastoma multiforme cells). Cytotoxicity was determined by measurement of 50% inhibition of cell growth by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The selectivity index (SI) was calculated for the investigated compounds. The

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• antiandrogen cancer treatment [8][9] (Figure 1). Moreover, aminosulfones remain a privileged scaffold in the ongoing development of new methods for the synthesis of pharmaceuticals [10][11][12], with multiple research compounds showing promising bioactivities such as MMP inhibition [13], antiinflammatory

• effects [14], сoagulation enzyme factor (FXa) inhibition [15] and antidepressant properties [16]. Considering the approaches to the synthesis of γ-aminosulfones, we focused our attention on the implementation of an aminoalkylation as a powerful and versatile tool for the synthesis of aliphatic amines [17

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• absorption (HIA), in vitro permeability to Caco-2 cells (Caco2), in vitro binding to plasma proteins (PPB), solubility, and inhibition of CYP2D6. The following were selected as descriptors of toxicity: carcinogenicity for rats and mice, mutagenicity according to the Ames test, and cardiotoxicity by

• inhibition of hERG in vitro. The results are shown in Supporting Information File 1, Table S5. As can be seen from the table, the obtained results suggest that the compounds have a good intestinal absorption and medium permeability. However they are expected to have low plasma protein binding and permeation

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• vivo using the diffusion-in-agar method [49] against Escherichia coli ΔtolC and E. coli lptD mutant strains. None of the compounds exhibited activity against the lptD mutant. Compound 12a showed the broadest growth inhibition zone, with compounds 9c and 13a also demonstrating significant effects

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• as a potent inhibitor of ornithine decarboxylase, the key enzyme that catalyzes the first step in polyamine biosynthesis [6]. This inhibition underlies both its therapeutic utility and its importance as a biochemical probe. From a structural standpoint, DFMO provides an intriguing case study for

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• ), Bipolaris sorokiniana (B.s., ascomycete causing root rot and spot blotch), and Sclerotinia sclerotiorum (S.s., ascomycete affecting sunflower, potato, and other cultures). The degree of mycelium growth inhibition on potato-sucrose agar amended with the studied compounds (30 mg/L) was used as the criterion

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• confirmed its mode of action by inhibition of the hedgehog signaling pathway, which plays a critical role in the differentiation and symmetry in the development of embryos [35]. We will have a further look into four different approaches to synthesize this natural product. The first synthesis was reported by

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• evaluation and structure–activity relationship studies. The systematic investigation of the their key biological activities, including estrogenic activity (assessed via breast cell proliferation assays), antitumor activity (evaluated through HeLa cell inhibition assays), and antibacterial activity (evaluated

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• mechanisms including elevation of reactive oxygen species (ROS) or interference with redox homeostasis, and inhibition of kinase or topoisomerase activities essential for cancer cell proliferation. The selective activity of thiouronium salts against cancer cells compared to non-malignant cells can be related

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• 2012, Lin and co-workers [69] isolated the membrane diterpenoid (−)-134 from the marine soft coral Sinularia pavida. The study showed that (−)-134 exhibits highly selective inhibition against the human promyelocytic leukemia cell line HL-60 with an IC50 of 2.7 μg/mL. Structurally, (−)-134 contains a