Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Synthesis and Anticancer Activities of Novel Bis-chalcones Incorporating the 1,3-diphenyl-1H-pyrazole Moiety: In Silico and In Vitro Studies

Author(s): Magda F. Mohamed, Farid M. Sroor*, Shahinda E. Elsayed, Karima F. Mahrous, Lamiaa Mageed, Mahmoud Khaled Hanafy, Sherif A. Ibrahim, Ahmed H. M. Elwahy* and Ismail A. Abdelhamid*

Volume 19, Issue 11, 2022

Published on: 12 May, 2022

Page: [1007 - 1021] Pages: 15

DOI: 10.2174/1570180819666220301151631

Price: $65

Abstract

A new series of bis-chalcones 5-10 has been prepared by the condensation reaction of one equivalent of bis(acetophenones) 3a-f with two equivalents of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde 4. The newly prepared compounds 5-10 have been fully characterized and evaluated as in vitro anticancer agents against a panel of human cancer cell lines A431, A549, PC3, and a normal human skin fibroblast BJ1.

Aims: The current work is designed to explore the anti-cancer activity of novel bis-chalcones incorporating a 1,3-diphenyl-1H-pyrazole moiety.

Background: Chalcones represent one of the most important organic compounds that have been attracting the interest of many researchers in drug discovery.

Objective: The present study was carried out to explore anti-cancer activity of novel bis-chalcones incorporating a 1,3-diphenyl-1H-pyrazole moiety as in vitro and in silico studies.

Materials and Methods: We used the condensation reaction to prepare bis-chalcones incorporating 1,3- diphenyl-1H-pyrazole moiety. The MTT Assay, Anti-cancer activity, Gene expression, DNA Fragmentation, DNA Damage, and Molecular docking were investigated.

Results: Compounds 5 and 9 were found to be the most promising compounds in the prepared series with IC50 (50.3 and 50.1 μg/ml, respectively) against epidermoid cancer cell line A431 compared to doxorubicin as a reference drug.

Conclusion: All of these results showed that chalcones 5 and 9 have promising anti-cancer properties without cytotoxic effect, which could make them a promising active component for further studies.

Keywords: Chalcones, anti-cancer, DNA damage, DNA fragmentation, gene expression, molecular docking study.

Next »
Graphical Abstract

[1]
Sahu, N.K.; Balbhadra, S.S.; Choudhary, J.; Kohli, D.V. Exploring pharmacological significance of chalcone scaffold: A review. Curr. Med. Chem., 2012, 19(2), 209-225.
[http://dx.doi.org/10.2174/092986712803414132] [PMID: 22320299]
[2]
Zhuang, C.; Zhang, W.; Sheng, C.; Zhang, W.; Xing, C.; Miao, Z. Chalcone: A Privileged structure in medicinal chemistry. Chem. Rev., 2017, 117(12), 7762-7810.
[http://dx.doi.org/10.1021/acs.chemrev.7b00020] [PMID: 28488435]
[3]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci., 2016, 5, e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[4]
Nielsen, S.F.; Boesen, T.; Larsen, M.; Schønning, K.; Kromann, H. Antibacterial chalcones-bioisosteric replacement of the 4′-hydroxy group. Bioorg. Med. Chem., 2004, 12(11), 3047-3054.
[http://dx.doi.org/10.1016/j.bmc.2004.03.071] [PMID: 15142563]
[5]
Mellado, M.; Espinoza, L.; Madrid, A.; Mella, J.; Chávez-Weisser, E.; Diaz, K.; Cuellar, M. Design, synthesis, antifungal activity, and structure-activity relationship studies of chalcones and hybrid dihydrochromane-chalcones. Mol. Divers., 2020, 24(3), 603-615.
[http://dx.doi.org/10.1007/s11030-019-09967-y] [PMID: 31161394]
[6]
Aoki, N.; Muko, M.; Ohta, E.; Ohta, S. C-geranylated chalcones from the stems of Angelica keiskei with superoxide-scavenging activity. J. Nat. Prod., 2008, 71(7), 1308-1310.
[http://dx.doi.org/10.1021/np800187f] [PMID: 18558745]
[7]
Maria, K.; Dimitra, H-L.; Maria, G. Synthesis and anti-inflammatory activity of chalcones and related Mannich bases. Med. Chem., 2008, 4(6), 586-596.
[http://dx.doi.org/10.2174/157340608786242070] [PMID: 18991744]
[8]
Israf, D.A.; Khaizurin, T.A.; Syahida, A.; Lajis, N.H.; Khozirah, S. Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-kappaB nuclear translocation and Ikappa-B phosphorylation in RAW 264.7 macrophage cells. Mol. Immunol., 2007, 44(5), 673-679.
[http://dx.doi.org/10.1016/j.molimm.2006.04.025] [PMID: 16777230]
[9]
Wu, J.; Li, J.; Cai, Y.; Pan, Y.; Ye, F.; Zhang, Y.; Zhao, Y.; Yang, S.; Li, X.; Liang, G. Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents. J. Med. Chem., 2011, 54(23), 8110-8123.
[http://dx.doi.org/10.1021/jm200946h] [PMID: 21988173]
[10]
Nowakowska, Z. A review of anti-infective and anti-inflammatory chalcones. Eur. J. Med. Chem., 2007, 42(2), 125-137.
[http://dx.doi.org/10.1016/j.ejmech.2006.09.019] [PMID: 17112640]
[11]
Ko, H-H.; Tsao, L-T.; Yu, K-L.; Liu, C-T.; Wang, J-P.; Lin, C-N. Structure-activity relationship studies on chalcone derivatives. the potent inhibition of chemical mediators release. Bioorg. Med. Chem., 2003, 11(1), 105-111.
[http://dx.doi.org/10.1016/S0968-0896(02)00312-7] [PMID: 12467713]
[12]
Yamamoto, T.; Yoshimura, M.; Yamaguchi, F.; Kouchi, T.; Tsuji, R.; Saito, M.; Obata, A.; Kikuchi, M. Anti-allergic activity of naringenin chalcone from a tomato skin extract. Biosci. Biotechnol. Biochem., 2004, 68(8), 1706-1711.
[http://dx.doi.org/10.1271/bbb.68.1706] [PMID: 15322354]
[13]
Cho, S.; Kim, S.; Jin, Z.; Yang, H.; Han, D.; Baek, N-I.; Jo, J.; Cho, C-W.; Park, J-H.; Shimizu, M.; Jin, Y-H. Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects. Biochem. Biophys. Res. Commun., 2011, 413(4), 637-642.
[http://dx.doi.org/10.1016/j.bbrc.2011.09.026] [PMID: 21945440]
[14]
Sato, Y.; He, J-X.; Nagai, H.; Tani, T.; Akao, T. Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis roots, acts in the lower part of intestine. Biol. Pharm. Bull., 2007, 30(1), 145-149.
[http://dx.doi.org/10.1248/bpb.30.145] [PMID: 17202675]
[15]
Birari, R.B.; Gupta, S.; Mohan, C.G.; Bhutani, K.K. Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: Experimental and computational studies. Phytomedicine, 2011, 18(8-9), 795-801.
[http://dx.doi.org/10.1016/j.phymed.2011.01.002] [PMID: 21315569]
[16]
Chen, M.; Christensen, S.B.; Blom, J.; Lemmich, E.; Nadelmann, L.; Fich, K.; Theander, T.G.; Kharazmi, A.; Licochalcone, A. Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob. Agents Chemother., 1993, 37(12), 2550-2556.
[http://dx.doi.org/10.1128/AAC.37.12.2550] [PMID: 8109916]
[17]
Go, M.L.; Wu, X.; Liu, X.L. Chalcones: An update on cytotoxic and chemoprotective properties. Curr. Med. Chem., 2005, 12(4), 481-499.
[http://dx.doi.org/10.2174/0929867053363153] [PMID: 15720256]
[18]
Synthesis of dihydroxylated chalcone derivatives with diverse substitution patterns and their radical scavenging ability toward DPPH free radicals. Bull. Korean Chem. Soc., 2008, 29(6), 1125-1130.
[http://dx.doi.org/10.5012/bkcs.2008.29.6.1125]
[19]
Liu, M.; Wilairat, P.; Croft, S.L.; Tan, A.L-C.; Go, M-L. Structure-activity relationships of antileishmanial and antimalarial chalcones. Bioorg. Med. Chem., 2003, 11(13), 2729-2738.
[http://dx.doi.org/10.1016/S0968-0896(03)00233-5] [PMID: 12788347]
[20]
Satyanarayana, M.; Tiwari, P.; Tripathi, B.K.; Srivastava, A.K.; Pratap, R. Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines. Bioorg. Med. Chem., 2004, 12(5), 883-889.
[http://dx.doi.org/10.1016/j.bmc.2003.12.026] [PMID: 14980600]
[21]
Chiaradia, L.D.; Mascarello, A.; Purificação, M.; Vernal, J.; Cordeiro, M.N.S.; Zenteno, M.E.; Villarino, A.; Nunes, R.J.; Yunes, R.A.; Terenzi, H. Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA. Bioorg. Med. Chem. Lett., 2008, 18(23), 6227-6230.
[http://dx.doi.org/10.1016/j.bmcl.2008.09.105] [PMID: 18930396]
[22]
Wu, J-H.; Wang, X-H.; Yi, Y-H.; Lee, K-H. Anti-AIDS agents 54. A potent anti-HIV chalcone and flavonoids from genus Desmos. Bioorg. Med. Chem. Lett., 2003, 13(10), 1813-1815.
[http://dx.doi.org/10.1016/S0960-894X(03)00197-5] [PMID: 12729671]
[23]
Domínguez, J.N.; Charris, J.E.; Lobo, G.; Gamboa de Domínguez, N.; Moreno, M.M.; Riggione, F.; Sanchez, E.; Olson, J.; Rosenthal, P.J. Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity. Eur. J. Med. Chem., 2001, 36(6), 555-560.
[http://dx.doi.org/10.1016/S0223-5234(01)01245-4] [PMID: 11525846]
[24]
Dimmock, J.R.; Elias, D.W.; Beazely, M.A.; Kandepu, N.M. Bioactivities of chalcones. Curr. Med. Chem., 1999, 6(12), 1125-1149.
[PMID: 10519918]
[25]
Guida, A.; Lhouty, M.H.; Tichit, D.; Figueras, F.; Geneste, P. Hydrotalcites as base catalysts.Kinetics of claisen-schmidt condensation, intramolecular condensation of acetonylacetone and synthesis of chalcone. Appl. Catal., 1997, 164(1-2), 251-264.
[26]
Gomes, M.N.; Muratov, E.N.; Pereira, M.; Peixoto, J.C.; Rosseto, L.P.; Cravo, P.V.L.; Andrade, C.H.; Neves, B.J. Chalcone derivatives: Promising starting points for drug design. Molecules, 2017, 22(8), 1210.
[http://dx.doi.org/10.3390/molecules22081210] [PMID: 28757583]
[27]
Srinivasan, B.; Johnson, T.E.; Lad, R.; Xing, C. Structure-activity relationship studies of chalcone leading to 3-hydroxy-4,3′,4′,5′-tetramethoxychalcone and its analogues as potent nuclear factor kappaB inhibitors and their anticancer activities. J. Med. Chem., 2009, 52(22), 7228-7235.
[http://dx.doi.org/10.1021/jm901278z] [PMID: 19883086]
[28]
Modzelewska, A.; Pettit, C.; Achanta, G.; Davidson, N.E.; Huang, P.; Khan, S.R. Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorg. Med. Chem., 2006, 14(10), 3491-3495.
[http://dx.doi.org/10.1016/j.bmc.2006.01.003] [PMID: 16434201]
[29]
Syam, S.; Abdelwahab, S.I.; Al-Mamary, M.A.; Mohan, S. Synthesis of chalcones with anticancer activities. Molecules, 2012, 17(6), 6179-6195.
[http://dx.doi.org/10.3390/molecules17066179] [PMID: 22634834]
[30]
Kamal, A.; Kashi Reddy, M.; Viswanath, A. The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs. Expert Opin. Drug Discov., 2013, 8(3), 289-304.
[http://dx.doi.org/10.1517/17460441.2013.758630] [PMID: 23317445]
[31]
Wei, H.; Ruan, J.; Zhang, X. Coumarin–chalcone hybrids: Promising agents with diverse pharmacological properties. RSC Advances, 2016, 6(13), 10846-10860.
[http://dx.doi.org/10.1039/C5RA26294A]
[32]
Kumar, D.; Kumar, N.M.; Akamatsu, K.; Kusaka, E.; Harada, H.; Ito, T. Synthesis and biological evaluation of indolyl chalcones as antitumor agents. Bioorg. Med. Chem. Lett., 2010, 20(13), 3916-3919.
[http://dx.doi.org/10.1016/j.bmcl.2010.05.016] [PMID: 20627724]
[33]
Sakai, T.; Eskander, R.N.; Guo, Y.; Kim, K.J.; Mefford, J.; Hopkins, J.; Bhatia, N.N.; Zi, X.; Hoang, B.H.; Flavokawain, B. A kava chalcone, induces apoptosis in synovial sarcoma cell lines. J. Orthop. Res., 2012, 30(7), 1045-1050.
[http://dx.doi.org/10.1002/jor.22050] [PMID: 22213202]
[34]
Nishimura, R.; Tabata, K.; Arakawa, M.; Ito, Y.; Kimura, Y.; Akihisa, T.; Nagai, H.; Sakuma, A.; Kohno, H.; Suzuki, T. Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma. Biol. Pharm. Bull., 2007, 30(10), 1878-1883.
[http://dx.doi.org/10.1248/bpb.30.1878] [PMID: 17917255]
[35]
Gacche, R.N.; Dhole, N.A.; Kamble, S.G.; Bandgar, B.P. In-vitro evaluation of selected chalcones for antioxidant activity. J. Enzyme Inhib. Med. Chem., 2008, 23(1), 28-31.
[http://dx.doi.org/10.1080/14756360701306370] [PMID: 18341249]
[36]
Zhang, H-J.; Qian, Y.; Zhu, D-D.; Yang, X-G.; Zhu, H-L. Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents. Eur. J. Med. Chem., 2011, 46(9), 4702-4708.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.016] [PMID: 21816517]
[37]
Meng, C.Q.; Ni, L.; Worsencroft, K.J.; Ye, Z.; Weingarten, M.D.; Simpson, J.E.; Skudlarek, J.W.; Marino, E.M.; Suen, K-L.; Kunsch, C.; Souder, A.; Howard, R.B.; Sundell, C.L.; Wasserman, M.A.; Sikorski, J.A. Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases. J. Med. Chem., 2007, 50(6), 1304-1315.
[http://dx.doi.org/10.1021/jm0614230] [PMID: 17323940]
[38]
Nowakowska, Z. Structural assignment of stilbenethiols and chalconethiols and differentiation of their isomeric derivatives by means of1H‐ and13C‐NMR spectroscopy. Spectrosc. Lett., 2005, 38(4-5), 477-485.
[http://dx.doi.org/10.1081/SL-200062816]
[39]
Miranda, C.L.; Stevens, J.F.; Ivanov, V.; McCall, M.; Frei, B.; Deinzer, M.L.; Buhler, D.R. Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones In Vitro. J. Agric. Food Chem., 2000, 48(9), 3876-3884.
[http://dx.doi.org/10.1021/jf0002995] [PMID: 10995285]
[40]
Won, S-J.; Liu, C-T.; Tsao, L-T.; Weng, J-R.; Ko, H-H.; Wang, J-P.; Lin, C-N. Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur. J. Med. Chem., 2005, 40(1), 103-112.
[http://dx.doi.org/10.1016/j.ejmech.2004.09.006] [PMID: 15642415]
[41]
Akihisa, T.; Tokuda, H.; Ukiya, M.; Iizuka, M.; Schneider, S.; Ogasawara, K.; Mukainaka, T.; Iwatsuki, K.; Suzuki, T.; Nishino, H. Chalcones, coumarins, and flavanones from the exudate of Angelica keiskei and their chemopreventive effects. Cancer Lett., 2003, 201(2), 133-137.
[http://dx.doi.org/10.1016/S0304-3835(03)00466-X] [PMID: 14607326]
[42]
Dhar Singh Yadav, L.; Kapoor, R. Nanoclay-catalyzed tandem conjugate addition-annulation protocol for imidazo-1,3-thiazines. Lett. Org. Chem., 2007, 4(3), 218-221.
[http://dx.doi.org/10.2174/157017807780737228]
[43]
Fathi, E.M.; Sroor, F.M.; Mahrous, K.F.; Mohamed, M.F.; Mahmoud, K.; Emara, M.; Elwahy, A.H.M.; Abdelhamid, I.A. Design, Synthesis, in silico and in vitro anticancer activity of novel bis‐furanyl‐chalcone derivatives linked through Alkyl spacers. ChemistrySelect, 2021, 6(24), 6202-6211.
[http://dx.doi.org/10.1002/slct.202100884]
[44]
Sroor, F.M.; Aboelenin, M.M.; Mahrous, K.F.; Mahmoud, K.; Elwahy, A.H.M.; Abdelhamid, I.A. Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents. Arch. Pharm. (Weinheim), 2020, 353(10), e2000069.
[http://dx.doi.org/10.1002/ardp.202000069] [PMID: 32657455]
[45]
Mohamed, M.F.; Sroor, F.M.; Ibrahim, N.S.; Salem, G.S.; El-Sayed, H.H.; Mahmoud, M.M.; Wagdy, M.M.; Ahmed, A.M.; Mahmoud, A.T.; Ibrahim, S.S.; Ismail, M.M.; Eldin, S.M.; Saleh, F.M.; Hassaneen, H.M.; Abdelhamid, I.A. Novel [l,2,4]triazolo[3,4-a]isoquinoline chalcones as new chemotherapeutic agents: Block IAP tyrosine kinase domain and induce both intrinsic and extrinsic pathways of apoptosis. Invest. New Drugs, 2021, 39(1), 98-110.
[http://dx.doi.org/10.1007/s10637-020-00987-2] [PMID: 32856275]
[46]
Abdelhamid, I.A.; Abdelmoniem, A.M.; Sroor, F.M.; Ramadan, M.A.; Ghozlan, S.A.S. Hantzsch-like one-pot three-component synthesis of heptaazadicyclopenta[a,j]anthracenes: A new ring system. Synlett, 2020, 31(09), 895-898.
[http://dx.doi.org/10.1055/s-0040-1708001]
[47]
Sroor, F.M.; Basyouni, W.M.; Tohamy, W.M.; Abdelhafez, T.H.; El-awady, M.K. Novel pyrrolo[2,3-d]pyrimidine derivatives: Design, synthesis, structure elucidation and In Vitro anti-BVDV activity. Tetrahedron, 2019, 75(51), 130749.
[http://dx.doi.org/10.1016/j.tet.2019.130749]
[48]
Tantawy, M.A.; Sroor, F.M.; Mohamed, M.F.; El-Naggar, M.E.; Saleh, F.M.; Hassaneen, H.M.; Abdelhamid, I.A. Molecular docking study, cytotoxicity, cell cycle arrest and apoptotic induction of novel chalcones incorporating thiadiazolyl isoquinoline in cervical cancer. Anticancer. Agents Med. Chem., 2020, 20(1), 70-83.
[http://dx.doi.org/10.2174/1871520619666191024121116] [PMID: 31696811]
[49]
Sroor, F.M.; Othman, A.M.; Tantawy, M.A.; Mahrous, K.F.; El-Naggar, M.E. Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives. Bioorg. Chem., 2021, 112, 104953.
[http://dx.doi.org/10.1016/j.bioorg.2021.104953] [PMID: 33964581]
[50]
Sroor, F.M.; Khatab, T.K.; Basyouni, W.M.; El-Bayouki, K.A.M. Synthesis and molecular docking studies of some new thiosemicarbazone derivatives as HCV polymeraseinhibitors. Synth. Commun., 2019, 49(11), 1444-1456.
[http://dx.doi.org/10.1080/00397911.2019.1605443]
[51]
Sroor, F.M.; Abdelmoniem, A.M.; Abdelhamid, I.A. Facile synthesis, structural activity relationship, molecular modeling and in vitro biological evaluation of new urea derivatives with incorporated isoxazole and thiazole moieties as anticancer agents. ChemistrySelect, 2019, 4(34), 10113-10121.
[http://dx.doi.org/10.1002/slct.201901415]
[52]
Sroor, F.M.; Basyouni, W.M.; Aly, H.F.; Ali, S.A.; Arafa, A.F. Design, synthesis and SAR of novel sulfonylurea derivatives for the treatment of Diabetes mellitus in rats. Med. Chem. Res., 2022, 31, 195-206.
[http://dx.doi.org/10.1002/ardp.202100381]
[53]
Kassab, R.M.; Elwahy, A.H.M.; Abdelhamid, I.A. 1,ω-Bis(formylphenoxy)alkane: Versatile precursors for novel bis-dihydropyridine derivatives. Monatsh. Chem., 2016, 147(7), 1227-1232.
[http://dx.doi.org/10.1007/s00706-015-1644-z]
[54]
Abdella, M.A.; H.M. Elwahy, A.; A. Abdelhamid, I. Multicomponent synthesis of novel bis(2-amino-tetrahydro-4H-chromene-3- carbonitrile) derivatives linked to arene or heteroarene cores. Curr. Org. Synth., 2016, 13(4), 601-610.
[http://dx.doi.org/10.2174/1570179413999151211115100]
[55]
Helmy, M.T.; Sroor, F.M.; Mahrous, K.F.; Mahmoud, K.; Hassaneen, H.M.; Saleh, F.M.; Abdelhamid, I.A.; Mohamed Teleb, M.A. Anticancer activity of novel 3-(furan-2-yl)pyrazolyl and 3-(thiophen-2-yl)pyrazolyl hybrid chalcones: Synthesis and in vitro studies. Arch. Pharm. (Weinheim), 2022, 355(3), e2100381.
[http://dx.doi.org/10.1002/ardp.202100381] [PMID: 34939695]
[56]
Salama, S.K.; Darweesh, A.F.; Abdelhamid, I.A.; Elwahy, A.H.M. Microwave assisted green multicomponent synthesis of novel bis(2-Amino-tetrahydro-4H-chromene-3-carbonitrile) derivatives using chitosan as eco-friendly basic catalyst. J. Heterocycl. Chem., 2017, 54(1), 305-312.
[http://dx.doi.org/10.1002/jhet.2584]
[57]
Abd El-Fatah, N.A.; Darweesh, A.F.; Mohamed, A.A.; Abdelhamid, I.A.; Elwahy, A.H.M. Experimental and theoretical study on the regioselective bis- and polyalkylation of 2-mercaptonicotinonitrile and 2-mercaptopyrimidine-5-carbonitrile derivatives. Tetrahedron, 2017, 73(11), 1436-1450.
[http://dx.doi.org/10.1016/j.tet.2017.01.047]
[58]
Shaaban, R.M.; H.M. Elwahy, A. Synthesis of Furo-, Pyrrolo-, and thieno-fused heterocycles by multi-component reactions (Part 1)&#8224. Curr. Org. Synth., 2013, 10(3), 425-466.
[http://dx.doi.org/10.2174/1570179411310030007]
[59]
Eid, E.M.; Hassaneen, H.M.E.; Abdelhamid, I.A.; Elwahy, A.H.M. Facile one‐pot, three‐component synthesis of novel bis(heterocycles) incorporating thieno[2,3‐b]thiophenes via Michael addition reaction. J. Heterocycl. Chem., 2020, 57(5), 2243-2255.
[http://dx.doi.org/10.1002/jhet.3945]
[60]
Darweesh, A.F.; Abd El-Fatah, N.A.; Abdelhamid, I.A.; Elwahy, A.H.M.; Salem, M.E. Investigation of the reactivity of (1H-benzo[d]imidazol-2-yl)acetonitrile and (benzo[d]thiazol-2-yl)acetonitrile as precursors for novel bis(benzo[4,5]imidazo[1,2-a]pyridines) and bis(benzo[4,5]thiazolo[3,2-a]pyridines). Synth. Commun., 2020, 50(16), 2531-2544.
[http://dx.doi.org/10.1080/00397911.2020.1784436]
[61]
Edqvist, P-H.D.; Fagerberg, L.; Hallström, B.M.; Danielsson, A.; Edlund, K.; Uhlén, M.; Pontén, F. Expression of human skin-specific genes defined by transcriptomics and antibody-based profiling. J. Histochem. Cytochem., 2015, 63(2), 129-141.
[http://dx.doi.org/10.1369/0022155414562646] [PMID: 25411189]
[62]
Kim, B-Y.; Lee, J.; Park, S.J.; Bang, O-S.; Kim, N.S. Gene expression profile of the A549 human non-small cell lung carcinoma cell line following treatment with the seeds ofdescurainia sophia, a potential anticancer drug. J. Evid. Based Complementary Altern. Med., 2013, 2013, 584604.
[63]
Olive, P.L.; Banáth, J.P.; Durand, R.E. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the “comet” assay. 1990. Radiat. Res., 2012, 178(2), AV35-AV42.
[http://dx.doi.org/10.1667/RRAV04.1] [PMID: 22870978]
[64]
Collins, A.; Dusinská, M.; Franklin, M.; Somorovská, M.; Petrovská, H.; Duthie, S.; Fillion, L.; Panayiotidis, M.; Raslová, K.; Vaughan, N. Comet assay in human biomonitoring studies: Reliability, validation, and applications. Environ. Mol. Mutagen., 1997, 30(2), 139-146.
[http://dx.doi.org/10.1002/(SICI)1098-2280(1997)30:2<139::AID-EM6>3.0.CO;2-I] [PMID: 9329638]
[65]
Yawata, A.; Adachi, M.; Okuda, H.; Naishiro, Y.; Takamura, T.; Hareyama, M.; Takayama, S.; Reed, J.C.; Imai, K. Prolonged cell survival enhances peritoneal dissemination of gastric cancer cells. Oncogene, 1998, 16(20), 2681-2686.
[http://dx.doi.org/10.1038/sj.onc.1201792] [PMID: 9632144]
[66]
Mohamed, M.F.; Samir, N.; Ali, A.; Ahmed, N.; Ali, Y.; Aref, S.; Hossam, O.; Mohamed, M.S.; Abdelmoniem, A.M.; Abdelhamid, I.A. Apoptotic induction mediated p53 mechanism and Caspase-3 activity by novel promising cyanoacrylamide derivatives in breast carcinoma. Bioorg. Chem., 2017, 73, 43-52.
[http://dx.doi.org/10.1016/j.bioorg.2017.05.012] [PMID: 28601699]
[67]
Lewis, W.S.; Cody, V.; Galitsky, N.; Luft, J.R.; Pangborn, W.; Chunduru, S.K.; Spencer, H.T.; Appleman, J.R.; Blakley, R.L. Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22. Kinetics, crystallography, and potential as selectable markers. J. Biol. Chem., 1995, 270(10), 5057-5064.
[http://dx.doi.org/10.1074/jbc.270.10.5057] [PMID: 7890613]
[68]
Richardson, C.M.; Williamson, D.S.; Parratt, M.J.; Borgognoni, J.; Cansfield, A.D.; Dokurno, P.; Francis, G.L.; Howes, R.; Moore, J.D.; Murray, J.B.; Robertson, A.; Surgenor, A.E.; Torrance, C.J. Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: Protein structure-guided design and SAR. Bioorg. Med. Chem. Lett., 2006, 16(5), 1353-1357.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.048] [PMID: 16325401]
[69]
Porter, J.; Payne, A.; de Candole, B.; Ford, D.; Hutchinson, B.; Trevitt, G.; Turner, J.; Edwards, C.; Watkins, C.; Whitcombe, I.; Davis, J.; Stubberfield, C. Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(1), 230-233.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.113] [PMID: 19027294]
[70]
Li, X.; Wang, J.; Condon, S.M.; Shi, Y. Structure of cIAP1-BIR3 and inhibitor. 2014.
[71]
Rew, Y.; Sun, D.; Yan, X.; Beck, H.P.; Canon, J.; Chen, A.; Duquette, J.; Eksterowicz, J.; Fox, B.M.; Fu, J.; Gonzalez, A.Z.; Houze, J.; Huang, X.; Jiang, M.; Jin, L.; Li, Y.; Li, Z.; Ling, Y.; Lo, M-C.; Long, A.M.; McGee, L.R.; McIntosh, J.; Oliner, J.D.; Osgood, T.; Saiki, A.Y.; Shaffer, P.; Wang, Y.C.; Wortman, S.; Yakowec, P.; Ye, Q.; Yu, D.; Zhao, X.; Zhou, J.; Medina, J.C.; Olson, S.H. Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the MDM2-p53 interaction. J. Med. Chem., 2014, 57(24), 10499-10511.
[http://dx.doi.org/10.1021/jm501550p] [PMID: 25384157]

© 2024 Bentham Science Publishers | Privacy Policy