Experimental investigation and molecular simulations of quinone related compounds as COX/LOX inhibitors.

Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer.

Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with proof.

New thymol-3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds , , , and displayed inhibitory activity against COX-2 (IC= 0.037, 0.

Imparting aromaticity to 2-pyridone derivatives by -alkylation resulted in new competitive and non-competitive PIM-1 kinase inhibitors with caspase-activated apoptosis.

New aromatic -alkyl pyridine derivatives were designed and synthesised as Proviral Integration Moloney (PIM)-1 kinase inhibitors. and showed potent anticancer activity against NFS-60, HepG-2, PC-3, and Caco-2 cell lines and low toxicity against normal human lung fibroblast Wi-38 cell line. Moreover, and induced apoptosis in the four tested cancer cell lines with high percentage.

Discovery of new pyridine-quinoline hybrids as competitive and non-competitive PIM-1 kinase inhibitors with apoptosis induction and caspase 3/7 activation capabilities.

New quinoline-pyridine hybrids were designed and synthesised as PIM-1/2 kinase inhibitors. Compounds , , , and showed low cytotoxicity against normal human lung fibroblast Wi-38 cell line and potent anticancer activity against myeloid leukaemia (NFS-60), liver (HepG-2), prostate (PC-3), and colon (Caco-2) cancer cell lines. In addition, and significantly induced apoptosis with percentage more than 66%.

Towards safer anti-inflammatory therapy: synthesis of new thymol-pyrazole hybrids as dual COX-2/5-LOX inhibitors.

New thymol - 1,5-disubstitutedpyrazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds , , and displayed inhibitory activity against COX-2 (IC= 0.043, 0.

Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes.

Colorectal cancer (CRC) is the second cause of cancer death worldwide. Inhibitors of COX-2, 5-LOX and PIM-1 kinase were very effective in the treatment and prevention of CRC in mouse models in vivo. Furthermore, thymol was confirmed to inhibit CRC cell proliferation in cancer cell lines and inhibitory activity against COX-2 and 5-LOX.

Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis.

We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their ICs, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity.

New pyrimidines and triazolopyrimidines as antiproliferative and antioxidants with cyclooxygenase-1/2 inhibitory potential.

Cyclooxygenase-2 (COX-2) inhibition and scavenging-free radicals are important targets in cancer treatment. Sulfanylpyrimidines and triazolopyrimidines were synthesized and evaluated as anticancer and antioxidant COX-1/2 inhibitors. Compound showed the same growth inhibitory activity as 5-fluorouracil against MCF-7.

Synthesis, antibacterial evaluation, and DNA gyrase inhibition profile of some new quinoline hybrids.

Antibiotic-resistant bacteria continue to play an important role in human health and disease. Inventive strategies are necessary to develop new therapeutic leads to challenge drug-resistance problems. From this perception, new quinoline hybrids bearing bioactive pharmacophores were synthesized.

Design, synthesis and docking study of pyridine and thieno[2,3-b] pyridine derivatives as anticancer PIM-1 kinase inhibitors.

A series of pyridine and thieno[2,3-b]pyridine derivatives have been designed and synthesized as anticancer PIM-1 kinase inhibitors. Thirty-seven compounds were selected by NCI to be tested initially at a single dose (10 µM) in the full NCI 60 cell line panel. Compound 5b showed potent anticancer activity and was tested twice in the five-dose assay which confirmed its potent antitumor activity (GI values 0.

Novel click modifiable thioquinazolinones as anti-inflammatory agents: Design, synthesis, biological evaluation and docking study.

Click chemistry was used to synthesize a new series of thioquinazolinone molecules equipped with propargyl moiety,1,2,3-triazolyl and isoxazolyl rings. Our design was based on merging pharmacophores previously reported to exhibit COX-2 inhibitory activities to a thioquinazolinone-privileged scaffold. The synthesized compounds were subjected to in vitro cyclooxygenase COX-1/COX-2 and 15-LOX inhibition assays.

New hybrid molecules combining benzothiophene or benzofuran with rhodanine as dual COX-1/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study.

New molecular hybrids combining benzothiophene or its bioisostere benzofuran with rhodanine were synthesized as potential dual COX-2/5-LOX inhibitors. The benzothiophene or benzofuran scaffold was linked at position -2 with rhodanine which was further linked to various anti-inflammatory pharmacophores so as to investigate the effect of such molecular variation on the anti-inflammatory activity. The target compounds were evaluated for their in vitro COX/LOX inhibitory activity.

New benzothiophene derivatives as dual COX-1/2 and 5-LOX inhibitors: synthesis, biological evaluation and docking study.

Aim: Simultaneous inhibition of 5-LOX/COX may enhance anti-inflammatory effects and reduce side effects. Hence, synthesis of novel dual inhibitors of 5-LOX/COX is an important strategy for treatment of inflammation. Results/methodology: The target compounds were designed to hybridize benzothiophene scaffold or its bioisostere benzofuran with various anti-inflammatory pharmacophore hetercycles through different atoms spacers.

Synthesis of novel benzofuran and related benzimidazole derivatives for evaluation of in vitro anti-HIV-1, anticancer and antimicrobial activities.

Previously, we synthesized and evaluated several benzofuran derivatives containing heterocyclic ring substituents linked to the benzofuran nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1, anticancer and antimicrobial agents. Among these derivatives, NSC 725612 and NSC 725716 exhibited interesting anti-HIV-1 activity. To further investigate the structure-activity relationship, we synthesized several new benzofuran derivatives derived from 2-acetylbenzofuran (2, 3a-c) and 2-bromoacetylbenzofuran (6; 7a,b; 8a,b).