Background: In response to the urgent need for continuous discovery of new anti-proliferative agents, a new series of quinazoline compounds was prepared.
Methods: As a reference, four cancer cell lines-HCT116, HePG2, Hela, and MCF-7-and sorafenib (SOR) were used to assess the novel motifs' in vitro anticancer efficacy. The most cytotoxic compounds were tested in a VEGFR-2 suppressive test and flow cytometric test.
In response to the urgent need for new anti-proliferative agents, four novel series of triazolopyrimidine compounds (7a-e, 9a-d, 11a-f, and 13a-e) were synthesized and evaluated for anticancer efficacy against HCT116, HeLa, and MCF-7 cell lines. Compound 13c emerged as the most potent, with IC values of 6.10, 10.
View Article and Find Full Text PDFDual targeting by a single molecule has emerged as a promising strategy for fighting cancer. In this study, a new set of 2-thioquinazolin-4(3)-ones as potential anti-cancer surrogates endowed with dual EGFR/VEGFR-2 kinases inhibitory activities were synthesized. The anti-tumor potency of the newly synthesized candidates 4-27 was evaluated against a panel of four cancer cell lines.
View Article and Find Full Text PDFCancer remains a leading cause of death worldwide, often resulting from uncontrolled growth in various organs. Protein kinase inhibitors represent an important class of targeted cancer therapies. Recently, the kinases BRAF and VEGFR-2 have shown synergistic effects on tumor progression.
View Article and Find Full Text PDFOrganic halogen compounds are cornerstones of applied chemical sciences. Halogen substitution is a smart molecular design strategy adopted to influence reactivity, membrane permeability and receptor interaction. Chiral bioreceptors may restrict the stereochemical requirements in the halo-ligand design.
View Article and Find Full Text PDFIn our study, a series of quinazoline-1,2,3-triazole hybrids (14a-r) have been designed and synthesized as multi-target EGFR, VEGFR-2, and Topo II inhibitors. All synthesized hybrids were assessed for their anticancer capacity. MTT assay revealed that compounds 14a, 14d, and 14k were the most potent hybrids against four cancer cell lines, HeLa, HePG-2, MCF-7, and HCT-116 at low micromolar range while exhibiting good selectivity against normal cell line WI-38.
View Article and Find Full Text PDFCisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling.
View Article and Find Full Text PDFIn an effort to develop new compounds for managing drug-induced liver injury, we prepared 23 novel hybrids based on 3-acetyl-11-keto-β-boswellic acid (AKBA) using various biocompatible linkers. A bioguided approach was employed to identify the most promising hybrid. Eight compounds exhibited superior anti-inflammatory activity compared to the parent compound.
View Article and Find Full Text PDFIn this study, we investigated the conjugation of theophylline with different compounds of natural origin hoping to construct new hybrids with dual activity against cholinergic and inflammatory pathways as potential agents for the treatment of Alzheimer's disease (AD). Out of 28 tested hybrids, two hybrids, acefylline-eugenol 6d and acefylline-isatin 19, were able to inhibit acetylcholinesterase (AChE) at low micromolar concentration displaying IC values of 1.8 and 3.
View Article and Find Full Text PDFThis research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid () was found to inhibit AR in a non-competitive manner (0.
View Article and Find Full Text PDFSARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery.
View Article and Find Full Text PDFThe low amount of metabolites isolated from natural products is one of the challenges preventing their biological evaluation. The modulation of biosynthetic pathways by stimulating stress-induced responses in plants was proven to be a valuable tool for diversification of already known natural products. Recently, we reported the dramatic effect of methyl jasmonate (MeJA) on alkaloids distribution.
View Article and Find Full Text PDFA new series of 2-aminobenzothiazole hybrids linked to thiazolidine-2,4-dione , 1,3,4-thiadiazole aryl urea and cyanothiouracil moieties was synthesised. The in vitro antitumor effect of the new hybrids was assessed against three cancer cell lines, namely, HCT-116, HEPG-2, and MCF-7 using Sorafenib (SOR) as a standard drug. Among the tested compounds, was the most potent showing IC50 of 5.
View Article and Find Full Text PDFMulti-target inhibitors represent useful anticancer agents with superior therapeutic attributes. Here in, two novel series of benzimidazole-triazole hybrids were designed, synthesised as multi-target EGFR, VEGFR-2 and Topo II inhibitors, and evaluated for anticancer activity. Compounds and were the most potent analogues against four cancer cell lines, HepG-2, HCT-116, MCF-7 and HeLa, and were further evaluated for EGFR, VEGFR-2, and Topo II inhibition.
View Article and Find Full Text PDFIn this work, the natural piperine moiety was utilised to develop two sets of piperine-based amides () and ureas () as potential anticancer agents. The anticancer action was assessed against triple negative breast cancer (TNBC) MDA-MB-231, ovarian A2780CP and hepatocellular HepG2 cancer cell lines. In particular, stood out as the most potent anti-proliferative analogue against TNBC MDA-MB-231 cells with IC equals 18.
View Article and Find Full Text PDFTwenty-five new hits of spirooxindole analogs engrafted with indole and pyrazole scaffolds were designed and constructed a [3+2]cycloaddition (32CA) reaction starting from three components: new chalcone-based indole and pyrazole scaffolds , substituted isatins , and secondary amines . The potency of the compounds were assessed in modulating cholinesterase (AChE) activity using Ellman's method. Compounds and showed the strongest acetylcholine esterase inhibition (AChEI) with IC values of 24.
View Article and Find Full Text PDFThe natural product piperine, the major bioactive alkaloid present in black pepper fruits, has the ability to modulate the functional activity of several biological targets. In this study, we have utilized the natural piperine as a tail moiety to develop new SLC-0111 analogues (6a-d, 8 and 9) as potential carbonic anhydrase inhibitors. Thereafter, different functionalities, free carboxylic acid (11a-c), acetyl (13a) and ethyl ester (13b-c), were exploited as bioisosteres of the sulfamoyl functionality.
View Article and Find Full Text PDFEleven compounds were isolated from the ethyl acetate extract of L endocarp, jezonofol , scirpusin A , cassigarol G , maackin A , threoguiacyl glycerol-8'-vanillic acid ether , erythroguiacyl glycerol-8'-vanillic acid ether , apigenin-7---D-glucoside , piceatannol , -hydroxy-benzoic acid , protocatechuic acid and vanillic acid . Compounds - were isolated for the first time from the plant. The isolated compounds were virtually screened against four critical components of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the main protease (M), papain-like protease (PL), nonstructural protein 13 (nsp13) and RNA dependent RNA polymerase (RdRp).
View Article and Find Full Text PDFCurcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin.
View Article and Find Full Text PDFEur J Med Chem
March 2020
In the present study, we report the design and synthesis of novel CAN508 sulfonamide-based analogues (4, 8a-e, 9a-h and 10a-e) as novel carbonic anhydrase (CA) inhibitors with potential CDK inhibitory activity. A bioisosteric replacement approach was adopted to replace the phenolic OH of CAN508 with a sulfamoyl group to afford compound 4. Thereafter, a ring-fusion approach was utilized to furnish the 5/5 fused imidazopyrazoles 8a-e which were subsequently expanded to 6/5 pyrazolopyrimidines 9a-h and 10a-e.
View Article and Find Full Text PDFAntioxidants (Basel)
September 2019
Hepatitis is an inflammatory condition that can develop hepatocellular carcinoma. Traditional medicine has always been the pillar of medical practice. However, it became less compatible with the current understanding of the diseases and the possible treatment.
View Article and Find Full Text PDFBackground And Aim: Traditional medicine is an important source for drug discovery. However, many challenges face the scientific community to develop novel drugs from it. To investigate the rationale behind the medical legacy of centuries of precious knowledge from traditional medicine, we aimed at performing virtual screening to identify potential leads from the middle-age textbook, The Canon of Medicine.
View Article and Find Full Text PDFIn an attempt to connect the legacy of centuries of invaluable knowledge from traditional medicine and the current understanding to the molecular mechanism of diseases, we took the advantage of the emergence of in silico screening as a promising tool for identification of potential leads from libraries of natural products. Traditional Chinese Medicine database was subjected to structure based virtual screening for identification of anti-inflammatory compounds using the 3D crystal structure of p38 alpha mitogen activated protein kinase. The molecular docking studies revealed the potential activity of several classes of compounds known to be the constituents of the rhizomes of Alpinia officinarum Hance (Lesser galangal).
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