Microwaves assisted synthesis of antitumor agents of novel azoles, azines, and azoloazines pendant to phenyl sulfone moiety and molecular docking for VEGFR-2 kinase

Shaaban, Mohamed R.; Farghaly, Thoraya A.; Alsaedi, Amani M. R.; Abdulwahab, Hanan Gaber

doi:10.1016/j.molstruc.2021.131657

Cited by 18 publications

(7 citation statements)

References 36 publications

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“…The method for synthesis of derivatives 6a-e, 10a-d, 14a, b, 15, and 16 as illustrated in Fig 2. PLOS ONE (M + , 3), 439 (5), 129 (19), 115 (53), 106 (18), 102 (20), 91 (100), 78 (10), 77 (27), 65 (24), 51 (7) (5), 129 (22), 115 (58), 106 (18), 102 (20), 91 (100), 77 (26), 65 (20), 51 (8) (5), 139 (6), 129 (34), 115 (100), 111 (92), 102 (37), 99 (29), 95 (5), 89 (20), 77 (14), 75 (36), 67 (37), 63 (27), 57 (7), 55 (7), 51 (11) (2), 210 (3), 141 (5), 129 (34), 115 (96), 111 (100), 102 (38), 99 (29), 89 (19), 77 (11), 75 (33), 71 (14), 67 (32), 63 (22), 51 (9) 12), 383 (24), 210 (4), 176 (45), 148 (9), 134 (100), 121 (12)<...…”

Section: The Reaction Of 2-(5-bromo-23-dihydro-1h-inden-1-ylidene)hyd...mentioning

confidence: 99%

“…13 C NMR (DMSO-d 6 ): 28.0 (CH 2 ), 28.4 (CH 2 ), 105.2, 120.9, 122.7, 123.5, 128.0, 129.1, 1 30.6, 132.0 134.4, 137.6, 150.7, 155.3, 169.9. MS(m/z): 463 (M + , 25), 461 (15), 256 (50), 210 (17), 182 (5), 174 (100), 155 (5), 146 (25), 133 (17), 129 (74), 120 (25), 115 (79), 102 (87), 95 (5), 89 (44), 75 (32), 63 (22), 57 (10), 51 (20) (21), 168 (19), 146 (5), 136 (5), 129 (30), 115 (42), 111 (12), 102 (59), 89 (25), 75 (21), 63 (10), 51 (5). Elemental Analysis (%): (C 18 H 13 BrClN 3 S; Mwt: 418.74).…”

Section: N-(5-bromo-indan-1-ylidene)-n'-[4-(4-bromo-phenyl)-thiazol-2...mentioning

confidence: 99%

“…1 H NMR(850 MHz, CDCl 3 ): 2.56 (s, 3H, CH 3 ), 2.78 (t, J = 8.5 Hz, 2H, CH 2 ), 3.16 (t, J = 8.5Hz, 2H, CH 2 ), 6.93 (t, J = 8.5Hz,1H, ArH), 7.17 (d, J = 8.5 Hz, 2H, ArH), 7.33 (t, J = 8.5Hz, 2H, ArH), 7.45-7.50 (m, 3H, ArH), 8.47 (s, 1H, NH), 11.62 (s, 1H, NH). MS(m/z): 384 (M + , 3), 212 (5), 210 (8), 176 (14), 115 (26), 105 (34), 102 (17), 92 (25), 77 (100), 70 (12) (45), 115 (59), 111 (100), 99 (45), 89 (16), 75 (40), 70 (27), 63 (23), 51 (10) MS(m/z): 463 (M + +2, 1), 462 (M + +1, 1), 461 (M + ,1), 147 (7), 129 (9), 120 (24), 115 (14), 107 (23), 102 (10), 92 (31), 77 (100), 65 (23), 51 (12)…”

Section: N'-(5-bromo-23-dihydro-1h-inden-1-ylidene)-2-oxo-n''-phenylp...mentioning

confidence: 99%

“…Despite the rapid advances in pharmacology and chemotherapeutic agents, the treatment of cancers remains a serious problem due to the toxicity, resistance, and lack selectivity of currently available anticancer drugs [4]. So far, the search is still going on for new compounds that are suitable and effective in treating different types of cancer [5][6][7][8]. On the other hand, nanoscale synthesis of heterocyclic materials is a scientific achievement due to its amazing applications in all medical and industrial fields [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

2023

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Two new series of thiazole and formazan linked to 5-Bromo-indan were synthesized, and their structures were assured based on all possible analytical techniques. The size of the tested derivatives was calculated from the XRD technique and found five derivatives 3, 10a, 14a, 15, and 16 on the nanosized scale. The two series were tested for their efficacy and toxicity as anti-colon and stomach cancers. Derivative 10d showed activity more than the two reference drugs used in the case of SNU-16. Surpislly, in the case of COLO205, five derivatives 4, 6c, 6d, 6e, and 10a are better than the two benchmarks used, and two derivatives, 14a and 14b more potent than cisplatin. All potent derivatives showed a strong fit with the active site of the two tested proteins (gastric cancer (PDB = 2BID) and colon cancer (PDB = 2A4L)) in the molecular docking study. The Pharmacophore and ADME studies of the new derivatives showed that most derivatives revealed promising bioactivity, which indicates the drug-likeness properties against kinase inhibitors, protease, and enzyme inhibitors. In addition, the ProTox-II showed that the four compounds 10d, 16, 6d, and 10a are predicted to have oral LD50 values ranging from 335 to 3500 mg/kg in a rat model with (1 s,4 s)-Eucalyptol bearing the highest values and quercetin holding the lowest one.

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Section: The Reaction Of 2-(5-bromo-23-dihydro-1h-inden-1-ylidene)hyd...mentioning

confidence: 99%

Section: N-(5-bromo-indan-1-ylidene)-n'-[4-(4-bromo-phenyl)-thiazol-2...mentioning

confidence: 99%

Section: N'-(5-bromo-23-dihydro-1h-inden-1-ylidene)-2-oxo-n''-phenylp...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

2023

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“…[21] Meanwhile, compounds carrying an arylsulfone moiety are widely synthesized [22][23][24][25][26] and known for their high biological activity and effectiveness in resisting many diseases. [27][28][29][30] Furthermore, P300 is considered as a significant histone acetyl-transferase; besides, its overexpression is usually directly related to cancer. It has become an attractive therapeutic target for cancer therapy, so development of new inhibitors of p300 has great importance in the treatment of cancer.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl–hydrazone derivatives as histone lysine acetyl‐transferase inhibitors and apoptosis inducers

Abbas

Farghaly

Sabour

et al. 2022

Archiv der Pharmazie

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Compounds containing both thiazole and arylsulfone moieties are recognized for their high biological activity and ability to fight a variety of ailments. Thus, in this context, new derivatives of (thiazol‐2‐yl)hydrazone with an arylsulfone moiety were synthesized as CPTH2 analogs with potent anti‐histone lysine acetyl‐transferase activity. Compounds 3, 4, 10b, and 11b showed an excellent inhibitory effect on P300 (E1A‐associated protein p300), compared to CPTH2. Among all the tested derivatives, compound 10b revealed the highest activity against both P300 and pCAF. In addition, the new hits were tested for anticancer efficacy against two leukemia cell lines. Most of them showed a moderate to potent antitumor effect on the k562 and CCRF‐CEM cell lines. Interestingly, the activity of compound 10b against the k562 cell line was found to be higher than that of CPTH2. Furthermore, it showed a good safety profile, better than CPTH2 on normal cells. Molecular docking analysis was carried out to reveal the crucial binding contacts in the inhibition of the P300 and pCAF enzymes.

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Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors

Farghaly

Abbas

Al‐Sheikh

et al. 2023

Drug Development Research

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With the aim of developing cyclin‐dependent kinase 2 (CDK2) inhibitors with strong antibreast cancer efficacy, new tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives were synthesized. The newly synthesized tri‐ and tetracyclic derivatives were achieved from the reaction of 4‐(4‐morpholin‐4‐yl‐phenyl)−1,3,4,5,6,7‐hexahydro‐benzo[6,7]cyclohepta[1,2‐d]pyrimidine‐2‐thione (5) with α‐haloketone derivatives as hydrazonyl chlorides, phenacyl bromide derivatives, chloroacetone, and ethyl substituted acetate derivatives. The MCF‐7 and MDA‐MB‐231 breast cancer cell lines were utilized to examine the anticancer properties. Compounds 5 and 8 were shown to be the most effective, with half‐maximal inhibitory concentration (IC50) values between 5.73 and 9.11 µM, which are on the level with doxorubicin. Mechanistic studies showed that 5 and 8 caused tumor cell death by inducing apoptosis and they also produced cancer arrest in the S phase of the cell cycle. In addition, compounds 5 and 8 showed strong anti‐CDK2 action (IC50 = 0.112 and 0.18 µM, respectively) comparable to roscovitine (IC50 = 0.127 µM). Moreover, the docking result demonstrated that derivatives 5 and 8 fit into the CDK2 active site in the proper orientation.

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Microwaves assisted synthesis of antitumor agents of novel azoles, azines, and azoloazines pendant to phenyl sulfone moiety and molecular docking for VEGFR-2 kinase

Cited by 18 publications

References 36 publications

Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

Indenyl-thiazole and indenyl-formazan derivatives: Synthesis, anticancer screening studies, molecular-docking, and pharmacokinetic/ molin-spiration properties

Design, synthesis, cytotoxicity, and molecular docking studies of novel thiazolyl–hydrazone derivatives as histone lysine acetyl‐transferase inhibitors and apoptosis inducers

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors

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