Design, Synthesis, Anti-Proliferative, and Apoptotic Assessment of Spirocyclopropyl Oxindole-Isatin Hybrids on Triple-Negative Breast Cancer.

A series of 1H-1,2,3-triazole-tethered spirocyclopropyl oxindole-isatin hybrids were synthesized using a copper-promoted click reaction and evaluated for their anti-proliferative activities against triple-negative breast cancer cell lines. The most potent compound in the series outperformed tamoxifen and 5-fluorouracil, with selectivity indices of 1.60 and 1.

Cu-promoted synthesis of triclosan-Mannich and Glaser adducts: anti-mycobacterial evaluation with validations.

 The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.

Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE - a molecular basis for domain selectivity.

Unlabelled: Angiotensin-1-converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight-binding inhibitor of ACE, K = 13.8 nm and 171.

The Dynamic Nonprime Binding of Sampatrilat to the C-Domain of Angiotensin-Converting Enzyme.

Sampatrilat is a vasopeptidase inhibitor that inhibits both angiotensin I-converting enzyme (ACE) and neutral endopeptidase. ACE is a zinc dipeptidyl carboxypeptidase that contains two extracellular domains (nACE and cACE). In this study the molecular basis for the selectivity of sampatrilat for nACE and cACE was investigated.

Chemical constituents from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae).

The chemical investigation of ethanolic extract from rhizomes of Cautleya spicata (Sm.) Baker (Zingiberaceae) has resulted in the isolation of eight compounds which were characterised as β-sitosterol (1), β-sitosterol β-D-glucoside (2), bergapten (3), zerumin A (4), (E)-labda-8(17),12-diene-15,16-dial (5), kaempferol (6), quercetin (7) and astragalin (8). All compounds were identified by spectroscopic and chemical methods.

Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2.

Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain.

Fragment-based design for the development of N-domain-selective angiotensin-1-converting enzyme inhibitors.

ACE (angiotensin-1-converting enzyme) is a zinc metallopeptidase that plays a prominent role in blood pressure regulation and electrolyte homeostasis. ACE consists of two homologous domains that despite similarities of sequence and topology display differences in substrate processing and inhibitor binding. The design of inhibitors that selectively inhibit the N-domain (N-selective) could be useful in treating conditions of tissue injury and fibrosis due to build-up of N-domain-specific substrate Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro).

New ketomethylene inhibitor analogues: synthesis and assessment of structural determinants for N-domain selective inhibition of angiotensin-converting enzyme.

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase containing two homologous domains. While the C-domain plays a major role in blood pressure regulation, the N-domain hydrolyzes the antifibrotic agent N-acetyl-Ser-Asp-Lys-Pro. Thus, N-domain selective (N-selective) inhibitors could be useful in the treatment of conditions relating to excessive tissue fibrosis.

Antibacterial sesquiterpene lactone glucoside from seed pods of Bauhinia retusa.

From the seed pods of Bauhinia retusa, a new eudesmane sesquiterpene glucoside, 1-O-β-D-glucopyranosyl-9β,15-dihydroxy-5α,6βH-eudesma-3-ene-6α,12-olide (1), has been isolated together with three known compounds, 4'-hydroxy-7-methoxy flavane (2), β-sitosterol (3), and stigmasterol (4). The structures of isolated compounds were verified with the help of 1D, 2D NMR, and HR-ESI-MS spectroscopies. Compound 1 showed moderate antibacterial activity against Pseudomonas aeruginosa and Escherichia coli when a disc diffusion method is used.

Chemical and antibacterial constituents of Skimmia anquetelia.

Investigation of the leaves of Skimmia anquetelia (Rutaceae) led to the isolation of a new coumarin glucoside 7,8-dihdroxy-6-[3'-beta- D-glucopyranosyloxy-2'(xi)-hydroxy-3'-methylbutyl]-coumarin ( 1) together with five known coumarins: 6-(2,3-dihydroxy-3-methylbutyl)-7-methoxycoumarin ( 2), skimmin ( 3), osthol ( 4), esculetin ( 5) and scopuletin ( 6). The antibacterial activity of compounds 1 and 3 was also investigated against the plant bacterial pathogens Agrobacterium tumifaciens, Pseudomonas syringae and Pactobacterium carotovorum. Structures were determined on the basis of analyses of spectral evidence including 1D, 2 D NMR (COSY, HMQC, HMBC and NOESY) and mass spectroscopy.