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Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene

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Abstract

The reaction of 2-amino-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene with chloroacetyl chloride gave the 2-chloroacetamido derivative 3. The latter reacted with hydrazine hydrate to give the hydrazine derivative 5 which was used to form the hydrazone derivatives 7a, b and 9a, b via its reaction with some carbonyl compounds. Moreover, it produced the pyrazole derivatives 11a, b through its reaction with either acetylacetone or ethyl acetoacetate. On the other hand, compounds 5 and 3 were used to form some thiazole, pyridine, and fused derivatives. The cytotoxicity of the newly obtained products was evaluated against some of the human cancer and normal cell lines where the results showed that compounds 3, 11b, 13, 18c, 18d, 21, 23, and 24 exhibited optimal cytotoxic effect against cancer cell lines, with IC50’s in the nM range.

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References

  • Abbas SE, Abdel Gawad NM, George RF, Akar YA (2013) Synthesis, antitumor and antibacterial activities of some novel tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. Eur J Med Chem 65:195–204

    Article  CAS  PubMed  Google Scholar 

  • Ament SMC, Gillissen F, Maessen JMC, Dirksen CD, Bell AVR, Vissers YL, Weijden TV, Meyenfeldt MF (2014) Sustainability of short stay after breast cancer surgery in early adopter hospitals. Breast 23:429–434

    Article  CAS  PubMed  Google Scholar 

  • Amr AE, Sherif MH, Assy MG, Al-Omar MA, Ragab I (2010) o Antiarrhythmic, serotonin antagonist and antianxiety activities of novel substituted thiophene derivatives synthesized from 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene-3-carboxamide. Eur J Med Chem 45:5935–5942

    Article  CAS  Google Scholar 

  • Aurelio L, Christopoulos A, Flynn BL, Scammells PJ, Sexton PM, Valant C (2011) The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes as allosteric modulators of the A1 adenosine receptor. Bioorg Med Chem Lett 21:3704–3807

    Article  CAS  PubMed  Google Scholar 

  • Behbehani H, Ibrahim HM, Makhseed S, Elnagdi MH, Mahmoud H (2012) 2-Aminothiophenes as building blocks in heterocyclic synthesis: Synthesis and antimicrobial evaluation of a new class of pyrido[1,2-a]thieno[3,2-e]pyrimidine, quinoline and pyridin-2-one derivatives. Eur J Med Chem 52:51–65

    Article  CAS  PubMed  Google Scholar 

  • Brayn B, Timothy M, Tore S (2009) General and applied toxicology, vol 6, 3rd edn. Wiley, New york, p 52

    Google Scholar 

  • Calleja MC, Persoone G (1992) The potential ofecotoxicological tests for the prediction of acute toxicityin man as evaluated on the 1st 10 chemicals on the meic program. ATLA 20:396–405

    Google Scholar 

  • Campaigne E (1984) Thiophenes and their benzo derivatives: (iii) synthesis and applications. Compreh Het Chem 4:863–934

    Article  Google Scholar 

  • Carballo JL, Inda ZLH, Pérez P, Grávalos MDG (2002) A comparison between two brine shrimp assays to detect in vitro cytotoxicity in marine natural products. BMC Biotechnol 2:17

    Article  PubMed Central  PubMed  Google Scholar 

  • Choudhary MI, Thomsen WJ (2001) Bioassay techniques for drug development. Harwood Academic Publishers, Amsterdam, pp 9–10

    Google Scholar 

  • Crouse KA, Chew KB, Tarafder MTH, Kasbollah A, Ali AM, Yamin BM, Fun HK (2004) Synthesis, characterization and bio-activity of S-2-picolyldithiocarbazate (S2PDTC), some of its Schiff bases and their Ni(II) complexes and X-ray structure of S-2-picolyl-β-N-(2-acetylpyrrole)dithiocarbazate. Polyhed 23:161–168

    Article  CAS  Google Scholar 

  • Dadiboyena S (2012) Recent advances in the synthesis of raloxifene: a selective estrogen receptor modulator. Eur J Med Chem 51:17–34

    Article  CAS  PubMed  Google Scholar 

  • Dewal MB, Wani AS, Vidaillac C, Oupický D, Rybak MJ, Firestine SM (2012) Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents. Eur J Med Chem 51:145–153

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Du QS, Shi YX, Lia PF, Zhao ZJ, Zhua WP, Qian XH, Li BJ (2013) Novel plant activators with thieno[2,3-d]-1,2,3-thiadiazole-6-carboxylate scaffold: Synthesis and bioactivity. Chin Chem Lett 24:967–969

    Article  CAS  Google Scholar 

  • Duval E, Case A, Stein RL, Cuny GD (2005) Structure–activity relationship study of novel tissue transglutaminase inhibitors. Bioorg Med Chem. Lett 15:1885–1889

    Article  CAS  PubMed  Google Scholar 

  • Fadda AA, Abdel-Latif EA, El-Mekawy RE (2009) Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives. Eur J Med Chem 44:1250–1256

    Article  CAS  PubMed  Google Scholar 

  • Ferreirra AP, da Silva JLF, Duarte MP, da Piedade MFM, Robalo MP, Harjivan SG, Marzano C, Gandin V, Marques MM (2009) Synthesis and characterization of new organometallic Benzo[b]thiophene derivatives with potential antitumor properties. Organometalics 28:5412–5423

    Article  Google Scholar 

  • Goncales CEP, Araldi D, Panatieri RB, Rocha JBT, Zeni G, Nogueira CW (2005) Antinociceptive properties of acetylenic thiophene and furan derivatives: evidence for the mechanism of action. Life Sci 76:2221–2234

    Article  CAS  PubMed  Google Scholar 

  • Goutham Vemana G, Kenneth G, Nepple KG, Joel Vetter J, Gurdarshan Sandhu G, Seth A, Strope SA (2014) Defining the potential of neoadjuvant chemotherapy use as a quality indicator for bladder cancer care. J Urol 192:43–49

    Article  PubMed  Google Scholar 

  • Leopoldo C, Baratto LC, Mariana V, Porsani MV, Ida C, Pimentel IC, Adaucto B, Pereira Netto AB, Reinhard Paschke R, Brás H, Oliveira BH (2013) Preparation of betulinic acid derivatives by chemical and biotransformation methods and determination of cytotoxicity against selected cancer cell lines. Eur J Med Chem 68:121–131

    Article  Google Scholar 

  • Madhusudana K, Shireesha B, Naidu VGM, Ramakrishna S, Narsaiah B, Rao AR, Diwan PV (2012) Anti-inflammatory potential of thienopyridines as possible alternative to NSAIDs. Eur J Pharmacol 678:48–54

    Article  CAS  PubMed  Google Scholar 

  • Mésangeau C, Fraise M, Delagrange P, Caignard DH, Boutin JA, Berthelot P, Yous S (2011) Preparation and pharmacological evaluation of a novel series of 2-(phenylthio)benzo[b]thiophenes as selective MT2 receptor ligands. Eur J Med Chem 46:1835–1840

    Article  PubMed  Google Scholar 

  • Mohareb RM, Al-Omran F (2012) Reaction of pregnenolone with cyanoacetylhydrazin Novel synthesis of hydrazide–hydrazone, pyrazole, pyridine, thiazole, thiophene derivatives and their cytotoxicity evaluations. Steroids 77:1551–1559

    Article  CAS  PubMed  Google Scholar 

  • Mohareb RM, El-Sayed NEE, Abdelaziz MA (2013) The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: Synthesis of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines. Steroids 78:1209–1219

    Article  CAS  PubMed  Google Scholar 

  • Padmavathi V, Reddy GD, Reddy SN, Mahesh K (2011) Synthesis and biological activity of 2-(bis((1,3,4-oxadiazolyl/1,3,4-thiadiazolyl)-methylthio)methylene)malononitriles. Eur J Med Chem 46:1367–1373

    Article  CAS  PubMed  Google Scholar 

  • Perspicace E, Hureaux VJ, Ragno R, Ballante F, Sartini S, Motta CL, Settimo FD, Chen B, Kirsch G, der Schnei S, Faivre B, Hesse S (2013) Design, synthesis and biological evaluation of new classes of thieno[3,2-d]pyrimidinone and thieno[1,2,3]triazine as inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2). Eur J Med Chem 63:765–781

    Article  CAS  PubMed  Google Scholar 

  • Pranati Samadder P, Yaozu XuY, Frank Schweizer F, Gilbert Arthur G (2014) Cytotoxic properties of D-gluco-, D-galacto- and D-manno-configured 2-amino-2-deoxy-glycerolipids against epithelial cancer cell lines and BT-474 breast cancer stem cells. Eur J Med Chem 78:225–235

    Article  PubMed  Google Scholar 

  • Refat HM, Fadda AA (2013) Synthesis and antimicrobial activity of some novel hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene derivatives. Eur J Med Chem 70:419–426

    Article  CAS  PubMed  Google Scholar 

  • Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Tolomeo M, Grimaudo S, Cristina AD, Pipitone MR, Balzarini J, Brancale A, Hamel E (2010) Substituted 2-(30,40,50- trimethoxybenzoyl)-benzo[b]thiophene derivatives as potent tubulin polymerization inhibitors. Bioorg Med Chem 18:5114–5122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Stephens CE, Felder TM, Sowell JW, Andrei G, Balzarini J, Snoeck R, Clercq ED (2001) Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of diarylsulfones. Bioorg Med Chem 9:1123–1132

    Article  CAS  PubMed  Google Scholar 

  • Titchenell PM, Showalter HD, Pons JF, Barber AJ, Jin Y, Antonetti DA (2013) Synthesis and structure–activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors. Bioorg Med Chem Lett 13:3034–3038

    Article  Google Scholar 

  • Upreti SR, Gurung S, Patel M, Dixit SM, Krause LK, Shakya G, Wannemuehler K, Rajbhandari R, Bohara R, Schluter WW (2014) Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal. Vaccine 32:4304–4309

    Article  CAS  PubMed  Google Scholar 

  • Vizzotto M, Porter W, Byrne D, Zevallos LC (2014) Polyphenols of selected peach and plum genotypes reduce cell viability and inhibit proliferation of breast cancer cells while not affecting normal cells. Food Chem 164:363–370

    Article  CAS  PubMed  Google Scholar 

  • Walker MJ, Mirea L, Glendon G, Ritvo P, Andrulis IL, Knight JA, Chiarelli AM (2014) Relevance date relevance—selected all access types all access types. Breast 23:482–488

    Article  PubMed  Google Scholar 

  • Wang W, Shangguan S, Qiu N, Hu C, Zhang L, Hu Y (2013) Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 1. Bioorg Med Chem 21:2879–2885

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

R M. Mohareb would like to express his deepest thanks for the Alexander von Humboldt foundation for affording a fellowship in Munich during Summer 2012 for doing research and completing this work.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Cairo University, Giza, A.R., Egypt

    Rafat M. Mohareb

  2. National Organization for Drug Control and Research, P.O. 29, Cairo, A.R., Egypt

    Wagnat W. Wardakhan & Faten I. Hamed

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  1. Rafat M. Mohareb
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  2. Wagnat W. Wardakhan
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  3. Faten I. Hamed
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Correspondence to Rafat M. Mohareb.

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Mohareb, R.M., Wardakhan, W.W. & Hamed, F.I. Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene. Med Chem Res 24, 2043–2054 (2015). https://doi.org/10.1007/s00044-014-1273-9

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  • DOI: https://doi.org/10.1007/s00044-014-1273-9

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