Synergy trap for guardian angels of DNA: Unraveling the anticancer potential of phthalazinone-thiosemicarbazone hybrids through dual PARP-1 and TOPO-I inhibition.

Targeting DNA repair, like PARP-1 and TOPO-I, shows promise in cancer therapy. However, resistance to single agents requires complex and costly combination strategies with significant side effects. Thus, there's an urgent need for single agents with dual inhibition.

Design and synthesis of quinazolin-4-one derivatives as potential anticancer agents and investigation of their interaction with RecQ helicases.

The upregulation of RecQ helicases has been associated with cancer cell survival and resistance to chemotherapy, making them appealing targets for therapeutic intervention. In this study, twenty-nine novel quinazolinone derivatives were designed and synthesized. The anti-proliferative activity of all compounds was evaluated against 60 cancer cell lines at the National Cancer Institute Developmental Therapeutic Program, with six compounds (11f, 11g, 11k, 11n, 11p, and 11q) being promoted to a five-dose screen.

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR, EGFR, and EGFR).

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for .

Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents.

Mutant isocitrate dehydrogenase (IDH) 2 "IDH2m" acquires a neo-enzymatic activity reducing α-ketoglutarate to an oncometabolite, D-2-hydroxyglutarate (2-HG). Three -triazine series were designed and synthesised using enasidenib as a lead compound. anticancer screening National Cancer Institute "NCI" revealed that analogues , , and were most potent, with mean growth inhibition percentage "GI%" = 66.

Dependence on linkers' flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents.

Herein we reported the design and synthesis of two series comprising twenty-two benzenesulfonamides that integrate the -triazine moiety. Target compounds successfully suppressed the hCA IX, with IC ranging from 28.6 to 871 nM.

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX.

Limited presence of hCA IX in normal physiological tissues and their overexpression only in solid hypoxic tumors made this isoform excellent possible target for developing new anticancer agents. We reported designing and synthesis of two novel series of benzenesulfonamides derivatives as hCA IX inhibitors bearing rigid cyclic linkers (1,3,5-dihydrotriazine in series A and 1,3,5-triazine in series B) in replace of traditional linear linkers. Also, novel cyanoethenyl spacer was assembled next to the 1,3,5-triazine linker in series B.

Discovery of new symmetrical and asymmetrical nitrile-containing 1,4-dihydropyridine derivatives as dual kinases and P-glycoprotein inhibitors: synthesis, assays, and studies.

Two new series of symmetric ( and asymmetric ( 1,4-DHP derivatives were designed, synthesised, and evaluated as anticancer agents. anticancer screening of target compounds National cancer institute "NCI" revealed that analogues , , and demonstrated antiproliferative action with mean growth inhibition percentage "GI%" = 41, 28, and 64, respectively. The reversal doxorubicin (DOX) effects of compounds , , and were examined and illustrated better cytotoxic activity with IC=1.

New Genetic Bomb Trigger: Design, Synthesis, Molecular Dynamics Simulation, and Biological Evaluation of Novel BIBR1532-Related Analogs Targeting Telomerase against Non-Small Cell Lung Cancer.

Telomeres serve a critical function in cell replication and proliferation at every stage of the cell cycle. Telomerase is a ribonucleoprotein, responsible for maintaining the telomere length and chromosomal integrity of frequently dividing cells. Although it is silenced in most human somatic cells, telomere restoration occurs in cancer cells because of telomerase activation or alternative telomere lengthening.

Discovery of new carbonic anhydrase IX inhibitors as anticancer agents by toning the hydrophobic and hydrophilic rims of the active site to encounter the dual-tail approach.

The hydrophobic and the hydrophilic rims in the active site of human carbonic anhydrase IX (hCA IX) which as well contains a zinc ion as part of the catalytic core, were simultaneously matched to design and synthesize potent and selective inhibitors using a dual-tail approach. Seventeen new compounds, 5a-q, were designed to have the benzenesulfonamide moiety as a zinc binding group. In addition, N-substituted hydrazone and N-phenyl fragments were chosen as the hydrophilic and hydrophobic parts, respectively to achieve favorable interactions with the corresponding halves of the active site.

Design, synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors.

Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines.

Design, synthesis, and bioactivity of dihydropyrimidine derivatives as kinesin spindle protein inhibitors.

A series of twenty-one 3,4-dihydropyrimidine derivatives bearing the heterocyclic 1,3-benzodioxole at position 4 in addition to different substituents at positions 2, 3 and 5 were designed and synthesized as monastrol analogs. The novel synthesized compounds were screened for their cytotoxic activity towards 60 cancer cell lines according to NCI (USA) protocol. Compounds 10b and 15 showed the best antitumor activity against most cell lines.

Synthesis, Evaluation of Pharmacological Activity, and Molecular Docking of 1,4-Dihydropyridines as Calcium Antagonists.

1,4-Dihydropyridine (DHP) is an important class of calcium antagonist. It inhibits the influx of extracellular Ca(2+) through L-type voltage-dependent calcium channels. Two series of nifedipine analogues were synthesized and evaluated as calcium antagonists.

Structure-based design, synthesis and preliminary evaluation of selective inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis.

Tuberculosis is an increasing threat, owing to the spread of AIDS and to the development of resistance of the causative organism, Mycobacterium tuberculosis, to the currently available drugs. Dihydrofolate reductase (DHFR) is an important enzyme of the folate cycle; inhibition of DHFR inhibits growth and causes cell death. The crystal structure of M.