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Finding effective and selective anticancer agents is a top medical priority due to high clinical treatment demand. However, current anticancer agents have serious side effects and resistance development remains a big concern. This creates an urgent need for new multitarget drugs that could solve these problems. Tetrahydrocarbazoles and 5-arylidene-4-thiazolinones have always attracted researchers for their multifaced anticancer activities and the possibility to be easily derivatized. Thereby, herein we report the combination of the two scaffolds to provide compounds 9a-j and 10a-j that were fully characterized and their tautomeric form was confirmed by crystal structure. 9a-j and 10a-j wereassessedfor invitro antiproliferative activityusing SRB assay against a panel of seven human cancer cell lines with doxorubicin as the standard. The results revealed that the cell lines derived from leukemia (Jurkat) and lymphoma (U937) are the most sensitive. Compounds 9d, 10e, 10g, and 10f revealed the highest potency (IC 50  = 3.11-11.89 μM) with much lower effects on normal lymphocytes cell line (IC 50  > 50 µM). The results show that modifications at 6th position of the THC and the nature of the substituent at the arylidene moiety affect the activity. To exploit the mode of action, 9d, 10e, 10f, and 10g were evaluated as VEGFR-2 and EGFR inhibitors. 10e is the most potent (IC 50 0.26 and 0.14 μM) against both enzymes. It also induced G0-G1-phase cell cycle arrest and apoptosis. While 10g exhibited higher potency (IC 50 9.95 μM) than vincristine (IC 50 15.63 μM) against tubulin. A molecular docking study was carried out to understand the interactions between 10e, 10g and their targets. This study reveals 10e and 10g as possible candidates for developing multitarget anticancer agents against leukemia and lymphoma., 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 © 2024 Elsevier Inc. All rights reserved.)

FimH is a mannose-recognizing lectin that is expressed by Escherichia coli guiding its ability to adhere and infect cells. It is involved in pathogenesis of urinary tract infections and Chron's disease. Several X-ray structure-guided ligand design studies were extensively utilized in the discovery and optimization of small molecule aryl mannoside FimH antagonists. These antagonists retain key specific interactions of the mannose scaffolds with the FimH carbohydrate recognition domains. Thiomannosides are attractive and stable scaffolds, and this work reports the synthesis of some of their new aryl and heteroaryl derivatives as FimH antagonists. FimH-competitive binding assays as well as biofilm inhibition of the new compounds (24-32) were determined in comparison with the reference n-heptyl α-d-mannopyranoside (HM). The affinity among these compounds was found to be governed by the structure of the aryl and heteroarylf aglycones. Two compounds 31 and 32 revealed higher activity than HM. Molecular docking and total hydrophobic to topological polar surface area ratio calculations attributed to explain the obtained biological results. Finally, the SAR study suggested that introducing an aryl or heteroaryl aglycone of sufficient hydrophobicity and of proper orientation within the tyrosine binding site considerably enhance binding affinity. The potent and synthetically feasible FimH antagonists described herein hold potential as leads for the development of sensors for detection of E. coli and treatment of its diseases., 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 © 2024 Elsevier Inc. All rights reserved.)

In our ongoing effort to investigate active specialised metabolites from genus Glandularia, phytochemical studies on the ethanolic extract of Glandularia × hybrida (Groenl. & Rümpler) G.L. Nesom & Pruski leaves resulted in the isolation of three undescribed compounds, a dibenzylbutyrolactolic lignan and two echinocystic acid based triterpenoid saponins, in addition to two known compounds. Interestingly, this study reports isolation of chemo-systematically valuable specialised metabolites for the first time from the genus under investigation. Additionally, the isolated metabolites were evaluated for their iNOS inhibition and cytotoxic activities using a combination of in silico and in vitro studies. The pharmacokinetics properties (ADMET) of some of the isolated compounds were determined using pkCSM-pharmacokinetics server. Molecular docking analysis showed that saponin compound possesses higher negative score (-9.59 kcal/mol) than the lignan compound (-6.56 kcal/mol). The isolated compounds also showed iNOS inhibition activity with IC 50 values ranging between 6.6 and 49.7 μM and significant cytotoxic activity against a series of cell lines including SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells. Hence, this study reveals that specialised metabolites from G. hybrida plant are of significant anti-inflammatory and cytotoxicity potentials., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A hybrid pharmacophore approach is used to design and synthesize two novel series of 2'-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC 50  = 0.037-0.041 µM) and 15-LOX (IC 50  = 1.41-1.80 µM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15-LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs., 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 © 2019 Elsevier Inc. All rights reserved.)