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• 22118-09-8 2-bromoacetyl chloride 
• 99-92-3 p-aminobenzophenone 
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Downstream Products

• 338426-56-5 N-(4-acetylphenyl)-2-[4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-[1,2,4]triazol-3-ylsulfanyl]acetamide 

Relevant academic research and scientific papers

Design, synthesis and antitrypanosomal activity of heteroaryl-based 1,2,4-triazole and 1,3,4-oxadiazole derivatives

Two series of novel 1,2,4-triazol-3-yl-thioacetamide 3a-b and 4a-b and 5-pyrazin-2-yl-3H-[1,3,4]oxadiazole-2-thiones 9a-h were designed and synthesized. The compounds prepared have been identified using 1H NMR, 13C NMR and elemental analyses. The synthesized compounds 3a, 3b, 4a, 4b, 9a, 9b, 9d-e and 9f have been evaluated with α-difluoromethylornithine (DFMO) as a control drug for their in vitro antitrypanosomal activity against Trypanosoma brucei. Results showed that 3b was the most active compound in general and also more potent than control DFMO. 3b was 8 folds more potent than the reference with IC50 of 0.79 μM and IC90 of 1.35 μM, respectively compared to DFMO (IC50 = 6.10 μM and IC90 of 8.66 μM). The tested compounds showed moderate cytotoxicity with selectivity indices ranging from 12 (9d) to 102 (3b) against L6 cells. Docking study was performed into ten of T. brucei enzymes which have been identified as potential/valid targets for most of the antitrypanosomal agents. The results of the docking study revealed high binding scores toward many of the selected enzymes. A good correlation was observed only between log (IC50) of antitrypanosomal activity of the new compounds and their calculated Ki values against TryR enzyme (R2 = 0.726). Compound 3b, the most active as antitrypanosomal agents exhibited similar binding orientation and interaction to those of WP6 against TryR enzyme. However, in a next round of work, a complementary studies will be carried out to clarify the mechanism of action of these compounds.

Design, synthesis, in vitro antiproliferative evaluation and in silico studies of new VEGFR-2 inhibitors based on 4-piperazinylquinolin-2(1H)-one scaffold

Angiogenesis is essential in the growth of solid tumors which need oxygen and nutrients supply to grow in size. The VEGF/VEGFR-2 signaling pathway plays an important role in tumor angiogenesis. Sorafenib is an FDA approved cancer therapeutic with activity

Synthesis and antimicrobial evaluation of new nitric oxide-donating fluoroquinolone/oxime hybrids

A new series of nitric oxide-donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling of Mycobacterium tuberculosis DNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes 3c–e are highly potent against Klebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 μM, respectively, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 μM, respectively). Notably, the antipseudomonal activities of compounds 2a and 4c were much higher than those of their respective parent fluoroquinolones.

Identification of N-phenyl-2-(phenylsulfonyl)acetamides/propanamides as new SLC-0111 analogues: Synthesis and evaluation of the carbonic anhydrase inhibitory activities

As a front-runner selective CA IX inhibitor currently in Phase Ib/II clinical trials, SLC-0111 has been herein exploited as a lead molecule for development of new different sets of N-phenyl-2-(phenylsulfonyl)acetamides/propanamides incorporating different functionalities; primary sulfonamide (5a-f), free carboxylic (8a, 8d), ethyl ester (8b, 8e), acetyl (8c, 8f) and nitro (10a, 10b), as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. All the prepared analogues have been examined for their CA inhibitory activities towards four human (h) isoenzymes, hCA I, II, IX and XII. Interestingly, replacement of SLC-0111 ureido linker with the flexible sulfonyl acetamide linker, as well as linker branching and elongation strategies successfully enhanced the inhibitory action toward hCA IX isoform, such as in sulfones 5a-d and 5f which displayed better activity than SLC-0111. Furthermore, sulfonamide-based sulfone (5f) and carboxylic acid-based sulfones (8a and 8d) demonstrated interesting selectivity toward the tumor-related hCA IX isoform over both hCA I and hCA II, which suggests them as promising candidates for further development as potential anticancer candidates. Thereafter, the anti-proliferative action for sulfones 5f, 8a and 8d was examined against breast (MCF-7) and colon (HCT-116) cancer cell lines. Also, sulfone 5f was further assessed for its impact on the cell cycle progression and apoptosis in HCT-116 cells.

NO-releasing STAT3 inhibitors suppress BRAF-mutant melanoma growth

Constitutive activation of STAT3 can play a vital role in the development of melanoma. STAT3-targeted therapeutics are reported to show efficacy in melanomas harboring the BRAFV600E mutant and also in vemurafenib-resistant melanomas. We designed and synthesized a series of substituted nitric oxide (NO)-releasing quinolone-1,2,4-triazole/oxime hybrids, hypothesizing that the introduction of a STAT3 binding scaffold would augment their cytotoxicity. All the hybrids tested showed a comparable level of in vitro NO production. 7b and 7c exhibited direct binding to the STAT3-SH domain with IC50 of ～ 0.5 μM. Also, they abrogated STAT3 tyrosine phosphorylation in several cancer cell lines, including the A375 melanoma cell line that carries the BRAFV600E mutation. At the same time, they did not affect the phosphorylation of upstream kinases or other STAT isoforms. 7c inhibited STAT3 nuclear translocation in mouse embryonic fibroblast while 7b and 7c inhibited STAT3 DNA-binding activity in the A375 cell line. Their anti-proliferating activity is attributed to their ability to trigger the production of reactive oxygen species and induce G1 cell cycle arrest in the A375 cell line. Interestingly, 7b and 7c showed robust cell growth suppression and apoptosis induction in two pairs of BRAF inhibitor-na?ve (-S) and resistant (-R) melanoma cell lines containing a BRAF V600E mutation. Surprisingly, MEL1617-R cells that are known to be more resistance to MEK inhibition by GSK1120212 than MEL1617-S cells exhibit a similar response to 7b and 7c.

Design, synthesis of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl)phenoxy)-N-arylacetamide derivatives: Evaluation of cytotoxic activity and molecular docking studies

In an attempt to discover potential cytotoxic agents, a series of novel (Z)-2-(3-(4-((3-benzyl-2,4-dioxothiazolidin-5-ylidene)methyl)-1-phenyl-1H-pyrazol-3-yl) phenoxy)-N-arylacetamide derivatives 11a-n were synthesized in varied steps with acceptable reaction procedures with good yields and characterized by 1H NMR, 13C NMR, IR and ESI-MS spectra. All the novel synthesized derivatives were assessed for their cytotoxic activity against human breast cell line (MCF-7) with different concentration of 0.625 μM, 1.25 μM, 2.5 μM, 5 μM and 10 μM respectively. Biological evaluation assay results were displayed in terms of percentage of cell viability reduction and IC50 values. Most of the screened derivatives demonstrated moderate to promising cytotoxic activity. Some of the derivatives, particularly compound 11d and 11n have shown promising cytotoxic activity with IC50 values 0.604 μM and 0.665 μM compared to standard drug cisplatin and compounds 11a, 11e and 11g also have shown considerable cytotoxic activity and the rest of the derivatives have shown moderate activity. Furthermore, molecular docking calculations and ADME properties of the synthesized molecules are in effective compliance with the cytotoxic evaluation results.

Design and synthesis of new 1,6-dihydropyrimidin-2-thio derivatives targeting VEGFR-2: Molecular docking and antiproliferative evaluation

A series of new 1,6-dihydropyrimidin-2-thiol derivatives (scaffold A) as VEGFR-2 inhibitors has been designed and synthesized. Compounds 3a, 3b, 3e and 4b have been selected for in vitro anticancer screening by the National Cancer Institute. Compound 3e showed remarkable anticancer activity against most of the cell lines tested, where a complete cell death against leukemia, non-small cell lung cancer, colon, CNS, melanoma, and breast cancer cell lines was observed. In vitro five dose tests showed that compound 3e had high activity against most of the tested cell lines with GI50 ranging from 19 to 100 μM and selectivity ratios ranging between 0.75 and 1.71 at the GI50 level. VEGFR-2-kinase was tested against 3a, 3b, 3e, 4b and sorafenib was used as a reference. Compounds 3a and 3e were the most potent analogues with IC50 values of 386.4 nM and 198.7 nM against VEGFR-2, respectively, in comparison to sorafenib (IC50 = 0.17 nM). The results of the docking study showed a good fitting of the new compounds to the active site of VEGFR-2 with binding free energies in the range of ?9.80 to ?11.25 kcal/mol compared to ?12.12 kcal/mol for sorafenib. Compounds 4a-e with the hydroxyimino group had a higher affinity to VEGFR-2 than their parent derivatives 3a-e.

Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents

A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 μM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners 6a-b and 9-16. Hydroxyimino-phenethyl scaffold compounds 17-24 were more active than the hydroxyimino-ethyl phenyl acetamide 7a-b derivatives. Compounds 18–20 and 22-24 exhibited inhibition of EGFR with IC50 ranging from 0.32 to 2.88 μM. Compounds 18-20 and 22-24 increased the level of active caspase 3 by 4–8 folds, compared to the control cells in Panc-1 cell lines compared to doxorubicin as a reference drug. Compounds 18, 22 and 23 were the most caspase-3 inducers. Compounds 22 and 23 increased the levels of caspase-8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of cytochrome c levels in Panc-1 human pancreas cancer cells. Compound 23 exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of Panc-1 cell line. The drug likeness profiles of compounds 18-20 and 22-24 were predicted to have good to excellent drug likeness profiles specially compounds 18-20 and 23. Finally molecular docking study was performed at the EGFR active site to suggest thier possible binding mode. The hydroxyimino-phenethyl scaffold compounds 17-24 represent an interesting starting point to optimize their pharmacokinetics and pharmacodynamics profiles.

Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors

A series of novel compounds carrying 1,2,4-triazole scaffold were prepared and evaluated for their antiproliferative activities against NCI 60 cell line. Compounds 10 (a, c), 11 (a-d), and 14 (a-e) were selected for evaluation at single concentration of 10 μM towards panel of sixty cancer cell lines. Some of nitric oxide (NO) donating triazole/oxime hybrids 11a-d showed antiproliferative activity better than their corresponding ketones. On the other hand, the thiazolo [3,2-b][1,2,4]-triazoles 14a-e showed remarkable antiproliferative activities against the same cell lines. Compound 14d was selected for five dose testing against the full panel of 60 human tumor cell lines. Compound 14d showed high selectivity against renal subpanel with selectivity ratio of 6.99 at GI50 level. Compounds 11a-d, 10a-d and 14a-e were tested against four cell lines using MTT assay then compounds of the least IC50 were evaluated against three known anticancer targets including EGFR, BRAF and Tubulin. The results revealed that compound 14d showed promising EGFR inhibitory activity of cancer cell proliferation and were also observed to be moderate BRAF and tubulin inhibitors. Moreover, cell cycle analysis and apoptosis assay were finished for compounds 14d and 14f. Finally molecular modeling studies were performed to explore the binding mode of the most active compounds to the target enzymes.

3-Aminomethyl pyridine chalcone derivatives: Design, synthesis, DNA binding and cytotoxic studies

Herein we report design, synthesis, and anticancer activity of compounds 6a–h and 11a–j. Compounds 6a–f were designed based on 3-aminomethyl pyridine attached to different acetamide derivatives and in compounds 6g–h it was attached to coumarin moiety. Coumarin containing compounds 6g–h showed very poor anticancer activity against both A549 (Lungs cancer cell line), and MCF-7 (Breast cancer cell line) cell lines in MTT assay. Compounds 11a–j were designed as derivatives of 3-aminomethyl pyridine and 4-amino chalcones. A series of chalcone derivatives of 3-aminomethyl pyridine 11a–j have been synthesized and screened for their in vitro anticancer activity and DNA binding affinity. Most of the compounds showed very good antimitotic activity against A549 cell line as compared to fluorouracil. Compounds 11g and 11i were selected for DNA-binding studies as they showed excellent activity against cancer cell lines in MTT assay. CT-DNA binding affinity of compounds 11g and 11i have been investigated by UV based DNA titration and fluorescence emission study against DNA-EtBr complex. Interestingly, compound 11i has displayed excellent antiproliferative activity, with IC50 0.0067?±?0.0002?μm, against MCF-7 cell line. Compound 11i has been studied for its cytotoxicity using MTT, LDH, as well as EtBr/AO assay and was found to induce apoptosis in the cancerous cell line.