Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• assays [36] (Figure 1A). In continuation of this work, these derivatives have also been investigated for their remarkable anti-HIV-1 activity [37] (Figure 1B). The same research group reported the synthesis of acetamide derivatives of pyrazolo-1,2-benzothiazines as anticancer drugs using a borane-THF

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• Maraviroc, an HIV-1 drug of the CCR5-receptor antagonists class that was approved by the FDA in 2007. In 2013, a significant work was published by Hoveyda and co-workers [6], who demonstrated that small organic molecules like hindered aminophenol 11 can serve as highly efficient and versatile catalysts in

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• (sEH) inhibitors [50], HIV-1 non-nucleoside reverse transcriptase inhibitors [51], or potential agents against visceral leishmaniasis [52] were found (Figure 8). Conclusion The Groebke–Blackburn–Bienaymé (GBB) reaction, a three-component condensation of amino heterocycles, aldehydes, and isonitriles

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• the purealidin bromotyrosine structure class, however, quorum sensing inhibition and antifouling activities against several strains of bacteria and microalgae appears in the literature [33][34], while HIV-1 replication inhibition and anti-Leishmania and Plasmodium activity has also been recorded [35

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• , several studies have shown that semisynthetic triterpenes with modifications at the C-3 and C-28 positions might have the potential to be anti-human immunodeficiency virus type-1 (HIV-1) drugs [24][25][26][27]. Bevirimat, a betulinic acid derivative modified at the C-3 position, demonstrated secure

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• )difluoromethyl group (ArSCF2) have potential biological applications such as anti-HIV-1 reverse transcriptase inhibitors and agrochemical applications [3][4]. Reurakul and Pohmakotr et al. carried out the reaction of PhSCF2Br with SmI2 in THF/iPrOH to generate PhSCF2 radicals followed by trapping with various

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ) appeared to be a more effective antiviral agent than AZT in PBM cells and U937 cells [13]. The BCH-189 core structure bears two stereocenters, and hence four stereoisomers are possible. The individual stereoisomers were also evaluated against HIV-1 activity in PBM cells and based on this study, it was

• -(−)-enantiomer 2, exhibits potential antiviral activity against HIV-1 (EC50 = 0.009 µM) in CEM cells. However, the corresponding ᴅ-(+)-enantiomer is less active against HIV-1 (EC50 = 0.84 µM) [15]. The fusion of an appropriate sugar element, carbacycle, or heterocyclic equivalent with an activated base results

• ), which may be responsible for such differences [24]. Initial results point at a conventional mechanism of action. Therein, the investigation of the cellular metabolism predicts triphosphate formation of the compounds by phosphorylation, and the resulting nucleotide is a selective inhibitor of the HIV-1

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• helix of the Antennapedia homeodomain) [167], Tat (14-amino acid peptide from HIV-1 TAT protein) [168], and transportan (chimeric 27-amino acid peptide derived from galanin and mastoparan) [169]. Corey and co-workers were the first to demonstrate that conjugation of an 11-mer PNA to penetratin peptide

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• receptor type 5 (CCR5), a HIV-1 coreceptor. We report herein a CCR5-selective RNA aptamer that acts to facilitate entry through a simplified BBB model and that drives the uptake of LNPs into CCR5-expressing cells, while the gp160 aptamer did not. We further observed that the addition of cell-penetrating

• the usefulness of aptamer-loaded LNPs to increase target cell specificity and potentially deliverability of central-nervous-system-active RNAi therapeutics across the BBB. Keywords: aptamer; blood–brain barrier; gene therapy; HIV-1; lipid nanoparticle; Introduction Lipid nanoparticles (LNPs

• across the blood–brain barrier (BBB) is critical. For example, despite successful implementation of antiretroviral drugs for the treatment of human immunodeficiency virus 1 (HIV-1), HIV-1-associated neurological disorders persist due to the poor uptake of antiretroviral drugs across the BBB [12][13][14

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• outshined by sulfonamides in medicinal chemistry, they have a large array of biologic activities that show promising effects as potent anti-HIV-1 [34], anti-hepatitis C [35], antifungal [36], insecticidal/acaricial [37] and antimalarial [38] agents. Results and Discussion We have previously reported the

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• attention for potential applications in host–guest recognition, such as gas storage and cationic complexation [31][32][33]. In the past years, the recognition of the biological and pharmaceutical relevance of fullerenes, such as their photodynamic activity, phototoxicity, HIV-1 protease inhibitor ability

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• ) have been reported to have antimicrobial [1], antifungal (e.g., tolnaftate and tolciclate) [2], antimycobacterial [3], human leucocyte elastase inhibitory [4], TRPV1 antagonistic [5], and PPARα1γ dual antagonistic [6] properties, and also act as intermediates in the syntheses of HIV-1 integrase ligands

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• applications as antibiotics [1], antiproliferative agents [2], anti-inflammatories [3] and antithrombotics [4]. They are also found in many bioactive natural products [5][6][7][8], some of which display anti-HIV-1 [9] and antimitotic activities [10], among others. Thiazolines also find use in organic synthesis

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• required to provide detailed explanation of this effect. Recently, a proof-of-principle for the application of hemi-indigo derivative Z-2 as a binder for the human immunodeficiency virus type 1 (HIV-1) RNA with photoswitchable fluorescent properties was provided [12]. It was shown that hemi-indigo Z-2

• associates with the regulatory elements of HIV-1 genome RNA with high affinity (Kb ≈ 105 M−1) while keeping its photoswitching properties. Both, the initial Z-2 and photoinduced E-2 forms remain bound to RNA. Most notably, the interaction of Z-2 with HIV-1 RNA produces a remarkable light-up effect whose

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• discovered, including HIV-1 reverse transcriptase inhibition activity [6][7][8][9][10][11]. Moreover, their utilization as highly regio- and stereoselective organocatalysts in specific types of chemical tranformations [12][13][14][15][16][17] was introduced, as well. More recently, O-thiocarbamates have been

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• caused by the hepatitis B virus (HBV) [3][4][5] and the herpes simplex virus (HSV, Figure 1) [5][6]. While 1 possesses inhibitory activity against the human immunodeficiency virus (HIV) [1][5], it has not been approved by the FDA for the treatment of HIV as the dose required to elicit inhibition can

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• the complex interactions between cells and pathogens, e.g., the human immunodeficiency virus (HIV-1) [6]. The HIV-1 envelope protein is present as a C3-symmetric trimer on the viruses’ surface [7], and the virus entry into the cell is mediated by its interactions with cellular receptors. To explore

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• ], quinolines are only present in approximately 2% of FDA approved prescription pharmaceuticals [2]. Recently, 2,3,4-trisubstituted arylquinolines such as BI 224436 1 [3][4] and 2 [5][6] have been shown to exhibit inhibitory activity against HIV-1 integrase that is essential for viral replication through

• [C13H12BrNO3 + Na]+ 331.989277; found: 331.988788; anal. calcd for C13H12BrNO3: C, 39.70; H, 1.67; found C, 39.51; H, 1.74. Investigational non-catalytic HIV-1 Integrase inhibitors. Boehringer Ingelheim retrosynthesis of quinoline 1. Quinoline ring condensation strategies. Isatoic anhydrides from anthranilic

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• ] or vasodilating activities (II) [6]. Other ones have been reported as inhibitors of HIV-1 integrase and viral replication in cells [7] or antitubercular agents (III) [8][9]. Various diarylmethane-based molecules, like tolterodine (IV) [10], podophyllotoxin (V) [11] and lasofoxifene (VI) [12] have

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• ]. Gottesfeld et al. synthesized a series of Py/Im HP-polyamide–DNA alkylator (chlorambucil) (HP-Chl) conjugates in order to bind and alkylate within the HIV-1 promoter region, thereby blocking HIV-1 replication and screened them against human colon carcinoma cell lines [74][75]. It has been observed that

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -aminopyrazolo[1,5-a]pyrimidine derivatives 155 (Scheme 43). All the synthesized compounds were screened for their anti-HIV activities in MT4 cell cultures and compound 155 (R1 = 2,4,6-trimethyl and R2 = 4-cyano) was found as most inhibiting for HIV-1 replication having an EC50 = 0.070 μM and the SI (selectivity

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• hypertension. Dihydropyridine derivatives are relatively vascular selective in their mechanism of action in lowering blood pressure [31][32]. Dimeric dihydropyridines are used as the precursors for HIV-1 protease inhibitors [33][34]. The furoxan system is used in the design of new NO donors [35][36][37][38][39

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• isomerization or epimerization, cyclic pseudopeptides using Fmoc SPPS [48][50]. Biological studies were conducted on monofluoroalkene-containing analogues of FC131, which is a known antagonist of the chemokine receptor CXCR4. The latter has implications in cancer metastasis and HIV 1 infection. Anti-HIV 1

• dipeptide isostere Lys-ψ[(Z)-CF=CH]-Lys into a fusion inhibitory peptide active against HIV 1, SC29EK, was investigated [49]. Weak to moderate anti-HIV activity was observed for the fluorinated analogues, but the potency was always lower than for SC29EK. This suggested than the H-bonding behaviour was

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• Brewer reviewed the role of density and number of glycan epitopes involved in multivalent carbohydrate interactions for legume lectins as well as for lectins of the innate immune system [74]. As an example, HIV-1 establishes multivalent contacts to DC-SIGN (E)-decorated dendritic cells in order to bypass

• host immune attack. Thus, DC-SIGN plays a key role in the dissemination of HIV-1 by capturing of HIV-1 at entry sites of infection and subsequent transport of the virus to CD4+ T cells in lymphoid tissues. The weak monovalent binding affinity of DC-SIGN (E) is compensated for by a multivalent display

• of oligomannosides on viral envelop glycoprotein gp120, facilitating stronger adhesion between dendritic cells and HIV-1 [43][75][76]. This multivalent binding interaction results in an enhancement in binding by several orders of magnitude, from a KD of 26 μM for monovalent Man9GlcNAc2, as compared