Yassin M. Nissan

Carbonic anhydrase inhibitors: Synthesis, molecular docking, cytotoxic and inhibition of the human carbonic anhydrase isoforms I, II, IX, XII with novel benzenesulfonamides incorporating pyrrole, pyrrolopyrimidine and fused pyrrolopyrimidine moieties

A series of novel pyrroles, pyrrolopyrimidines, pyrazolopyrrolopyrimidine, triazolopyrrolopyrimidines, tetrazolopyrrolopyrimidine, triazinopyrrolopyrimidines and pyrrolopyrimidotriazepines bearing the biologically active benzenesulfonamide moiety were synthesized by using pyrrole-o-amino-carbonitrile as key intermediate. All the synthesized compounds were evaluated for their in vitro carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects against the human (h) isoforms hCA I, II, IX and XII. Among the tested derivatives, compounds 16, 18 and 20-24 showed potent activity as inhibitors for the tumor associated transmembrane isoforms (hCA IX and XII) in the nanomolar and subnanomolar range, with high selectivity. All compounds underwent cytotoxic activity assays on human breast cancer cell line (MCF-7) showing effective activity, comparable to that of the clinically used drug doxorubicin.

Synthesis and anticancer activity of some novel trifluoromethylquinolines carrying a biologically active benzenesulfonamide moiety.

Several trifluoromethylquinoline derivatives containing a biologically active benzenesulfonamide moiety 2-14, 16, urea derivatives 15, 17, 4-isothiocyanate 18 and the corresponding carbamimidothioic acid derivatives 19-30, were synthesized from the strategic starting material 4-chloro-7-trifluoromethylquinoline 1. The structures of the newly synthesized compounds were elucidated on the basis of elemental and spectral analyses. All the prepared compounds were evaluated for their in vitro anticancer activity against various cancer cell lines. Most of the synthesized compounds showed good activity, especially compound 15 which exhibited higher activity than the reference drug doxorubicin. In order to suggest the mechanism of action for their cytotoxic activity, molecular docking for all synthesized compounds was done on the active site of PI3K and good results were obtained.

Novel sulfonamides bearing pyrrole and pyrrolopyrimidine moieties as carbonic anhydrase inhibitors: Synthesis, cytotoxic activity and molecular modeling.

Novel pyrrole and pyrrolopyrimidine scaffold-based sulfonamides were designed and synthesized. The carbonic anhydrase (CA) inhibition ability of all derivatives was assessed against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated isoforms hCA IX and XII. Some of these sulfonamides were 6-8 fold more potent than the reference drug acetazolamide (AZA, Ki = 5.7 nM)) against hCA XII showing subnanomolar activity. The in vitro cytotoxicity of these derivatives was evaluated against MCF-7, where some derivatives were more cytotoxic than doxorubicin (IC50 = 8.02 μM) displaying IC50 values between 6.46 and 7.56 μM. Docking of these sulfonamides with CA XII was performed and their binding modes were comparable with that of AZA.

Dapson in heterocyclic chemistry, part VIII: synthesis, molecular docking and anticancer activity of some novel sulfonylbiscompounds carrying biologically active 1,3-dihydropyridine, chromene and chromenopyridine moieties

Several new sulfonebiscompounds having a biologically active 1,2-dihydropyridine-2-one 3–19, acrylamide 20, chromene 21, 22 and chromenopyridine 23, 24 moieties were synthesized and evaluated as potential anticancer agents. The structures of the products were confirmed via elemental analyses and spectral data. The screening tests showed that many of the biscompounds obtained exhibited good anticancer activity against human breast cell line (MCF7) comparable to doxorubicin which was used as reference drug. Compounds 11, 17 and 24 showed IC50 values 35.40 μM, 29.86 μM and 30.99 μM, respectively. In order to elucidate the mechanism of action of the synthesized compounds as anticancer agents, docking on the active site of farnesyltransferase and arginine methyltransferase was also performed and good results were obtained.

Novel brominated quinoline and pyrimidoquinoline derivatives as potential cytotoxic agents with synergistic effects of γ-radiation

New quinoline derivatives 6, 7 and 19, pyrimidoquinoline derivatives 8–16 and triazolopyrimidoquinoline derivatives 17 and 18 bearing a bromo-substituent were synthesized starting from 3-(4-Bromophenylamino)-5,5-dimethylcyclohex-2-enone 3. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 9, 11, 17 and 18 showed IC50 values (36.4, 39.7, 39.02 and 36.4 μM, respectively) comparable to that of the reference drug doxorubicin (IC50 = 32.02 μM). On the other hand, compound 6, 14 and 19 exhibited better activity than doxorubicin with IC50 values of 8.5, 23.5 and 23.7 μM. Additionally, the most potent compounds 6, 14 and 19 were evaluated for their ability to enhance the cell killing effect of γ-radiation.

Synthesis, Molecular Docking, and Biological Evaluation of Some Novel Hydrazones and Pyrazole Derivatives as Anti-inflammatory Agents

2‐Hydrazinyl‐N‐(4‐sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4–10 and pyrazole derivatives 11–17. All compounds were tested for their in vivo anti‐inflammatory activity and their ability to inhibit the production of PGE2 in serum samples of rats. IC50 values for the most active compounds for inhibition of COX‐1 and COX‐2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX‐2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti‐inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15–17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX‐1/COX‐2 inhibition in vitro.

Synthesis and biological evaluation of new pyrazolone-pyridazine conjugates as anti-inflammatory and analgesic agents.

A new series of pyrazolone-pyridazine conjugates 3 and 4a-l were synthesized and characterized by spectroscopic means and elemental analyses. All compounds were tested in vivo for their anti-inflammatory and analgesic properties against diclofenac, as reference compound. The synthesized compounds were also evaluated for their ability to inhibit the production of certain inflammatory cytokines such as TNF-α and IL-6 in serum samples. The ulcerogenic potential of the synthesized compounds was also determined. IC50 values for inhibition of COX-1 and COX-2 enzymes were investigated in vitro for the most active candidates. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Among the synthesized derivatives, compounds 4c and 4e showed good analgesic and anti-inflammatory activities with lower ulcer index than the reference drug.

Design, synthesis and anticancer activity of some novel thioureido-benzenesulfonamides incorporated biologically active moieties

BackgroundMany thiourea derivatives have exhibited biological activities including anticancer activity through several mechanisms. On the other hand, benzenesulfonamide derivatives have proven to be good anticancer agents. Hybrids of both moieties could be further developed to explore their biological activity as anticancer.ResultsNovel series of thioureidobenzenesulfonamides incorporating miscellaneous biologically active moieties 3–17 were designed and synthesized utilizing 4-isothiocyanatobenzenesulfonamide 2 as strategic starting material. The structures of the newly synthesized compounds were established on the basis of elemental analyses, IR, 1H-NMR, 13C-NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against various cancer cell lines. Most of the synthesized compounds showed good activity, especially compounds 3, 6, 8, 9, 10, 15 and 16 which exhibited good activity higher than or comparable to the reference drugs, DCF and Doxorubicin, except breast cancer line. As a trial to suggest the mechanism of action of the active compounds, molecular docking on the active site of mitogen kinase enzyme (MK-2) was performed and good results were obtained especially for compound 3.ConclusionCompounds 3, 6, 8, 9, 10, 15 and 16 may represent good candidates for further biological investigations as anticancer agents. Their cytotoxic activity could be due to their action as MK-2 enzyme inhibitors.Graphical abstractCompound 3 on the active site of MK-2 enzyme

Novel chloroquinoline derivatives incorporating biologically active benzenesulfonamide moiety: synthesis, cytotoxic activity and molecular docking

BackgroundQuinoline derivatives have diverse biological activities including anticancer activity. On the other hand, many sulfonamide derivatives exhibited good cytotoxic activity. Hybrids of both moieties may present novel anticancer agents.ResultsChloroquinoline incorporating a biologically active benzene-sulfonamide moieties 5–21 and diarylsulfone derivatives 22 and 23 were prepared using (E)-1-(4-((E)-7-chloro-1-methylquinolin-4(1H)-ylideneamino)phenyl)-3-(dimethyl-amino)prop-2-en-1-one 4 as strategic starting material. The structure of the newly synthesized compounds were confirmed by elemental analyses and spectral data. Compound 4 was confirmed by X-ray crystallographic analysis. The prepared compounds were evaluated for their anticancer activity against Lung, HeLa, Colorectal and breast cancer cell lines. Compounds 2, 4, 7, 11, 14 and 17 showed better or comparable activity to 2′, 7′-dichlorofluorescein (DCF) as reference drug. Molecular docking of the active compounds on the active site of PI3K enzyme was performed in order to explore the binding mode of the newly synthesized compounds.ConclusionCompounds 2, 4, 7, 11, 14 and 17 are novel quinoline derivatives that may represent good candidates for further evaluations as anticancer agents. The mechanism of action of these compounds could be through inhibition of PI3K enzyme.Graphical abstractCompound 17 on the active site of PI3K

Novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl)-benzenesulfonamides as cytotoxic and radiosensitizing agents

A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene-sulfonamides were synthesized and screened for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC50 values markedly decreased to 11.9 μM, 11.7 μM, and 11.6 μM, respectively.