Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and anticancer properties of mono Mannich bases containing vanillin moiety

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

In this study, Mannich bases 2–8, 2-(3-or-5-aminomethyl-4-hydroxy-3-or-5-methoxybenzylidene)indan-1-one, were designed and synthesized starting from 2-(4-hydroxy-3-methoxybenzylidene)indan-1-one, 1. Synthesized compounds were tested against several tumor cell lines and non-tumor cells to evaluate the cytotoxicities of the compounds and to test whether the sequential cytotoxicity hypothesis works on the studied compounds. The data obtained from cytotoxicity tests pointed out that sequential cytotoxicity hypothesis worked on compounds 3 and 4 since they had higher potency selectivity expression values. The leader compound of the present study is compound 4, 2-(3-dipropylaminomethyl-4-hydroxy-5-methoxy-benzylidene)-indan-1-one, since it has the highest potency selectivity expression value among the compounds studied. This molecule can be the leader compound for further studies and designes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Fig. 1

Similar content being viewed by others

References

  • Bilginer S, Gul HI, Mete E, Das U, Sakagami H, Umemura N, Dimmock JR (2013) 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: a novel group of tumour-selective cytotoxins. J Enzyme Inhib Med Chem 28:974–980

    Article  CAS  PubMed  Google Scholar 

  • Das S, Das U, Michel D, Gorecki DK, Dimmock JR (2013) Novel 3,5-bis(arylidene)-4-piperidone dimers: potent cytotoxins against colon cancer cells. Eur J Med Chem 64:321–328

    Article  CAS  PubMed  Google Scholar 

  • Das U, Sharma RK, Dimmock JR (2009) 1,5-diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets. Curr Med Chem 16:2001–2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dimmock JR, Kumar P, Allen TM, Kao GY, Halleran S, Balzarini J, de Clercq E (1997) Synthesis and cytotoxic evaluation of some carbohydrazones and thiocarbohydrazones of various unsaturated ketones and related Mannich bases. Pharmazie 52:182–186

    CAS  PubMed  Google Scholar 

  • Gul HI, Calis U, Vepsalainen J (2004) Synthesis of some mono-Mannich bases and corresponding azine derivatives and evaluation of their anticonvulsant activity. Arzneimittelforschung 54:359–364

    CAS  PubMed  Google Scholar 

  • Gul HI, Gul M, Erciyas E (2003) Toxicity of some bis Mannich bases and corresponding piperidinols in the brine shrimp (Artemia salina) bioassay. J Appl Toxicol 23:53–57

    Article  CAS  PubMed  Google Scholar 

  • Gul HI, Gul M, Hanninen O (2002) Cytotoxic activities of some mono and bis Mannich bases derived from acetophenone in brine shrimp bioassay. Arzneimittelforschung Drug Res 52:840–843

    CAS  Google Scholar 

  • Gul HI, Ojanen T, Vepsalainen J, Gul M, Erciyas E, Hanninen O (2001a) Antifungal activity of some mono, bis and quaternary Mannich bases derived from acetophenone. Arzneimittelforschung 51:72–75

    CAS  PubMed  Google Scholar 

  • Gul HI, Sahin F, Gul M, Ozturk S, Yerdelen KO (2005a) Evaluation of antimicrobial activities of several mannich bases and their derivatives. Arch Pharm 338:335–338

    Article  CAS  Google Scholar 

  • Gul HI, Suleyman H, Gul M (2009) Evaluation of the anti-inflammatory activity of N,N’-bis(3-dimethylamino-1-phenyl-propylidene) hydrazine dihydrochloride. Pharm Biol 47:968–972

    Article  CAS  Google Scholar 

  • Gul HI, Tugrak M, Sakagami H (2015) Synthesis of some acrylophenones with N-methylpiperazine and evaluation of their cytotoxicities. J Enzyme Inhib Med Chem 31(1):147–151

    Article  PubMed  Google Scholar 

  • Gul HI, Yerdelen KO, Das U, Gul M, Pandit B, Li PK, Dimmock JR (2008) Synthesis and cytotoxicity of novel 3-aryl-1-(3’-dibenzylaminomethyl-4’-hydroxyphenyl)-propenones and related compounds. Chem Pharm Bull 56:1675–1681

    Article  CAS  PubMed  Google Scholar 

  • Gul HI, Yerdelen KO, Gul M, Das U, Pandit B, Li PK, Secen H, Sahin F (2007) Synthesis of 4’-hydroxy-3’-piperidinomethylchalcone derivatives and their cytotoxicity against PC-3 cell lines. Arch Pharm 340:195–201

    Article  CAS  Google Scholar 

  • Gul M, Atalay M, Gul HI, Nakao C, Lappalainen J, Hanninen O (2005b) The effects of some Mannich bases on heat shock proteins HSC70 and GRP75, and thioredoxin and glutaredoxin levels in Jurkat cells. Toxicol In Vitro 19:573–580

    Article  CAS  PubMed  Google Scholar 

  • Gul M, Gul HI, Das U, Hanninen O (2005c) Biological evaluation and structure-activity relationships of bis-(3-aryl-3-oxo-propyl)-methylamine hydrochlorides and 4-aryl-3-arylcarbonyl-1-methyl-4-piperidinol hydrochlorides as potential cytotoxic agents and their alkylating ability towards cellular glutathione in human leukemic T cells. Arzneimittelforschung 55:332–337

    CAS  PubMed  Google Scholar 

  • Gul M, Gul HI, Vepsalainen J, Erciyas E, Hanninen O (2001b) Effect of acetophenone derived Mannich bases on cellular glutathione level in Jurkat cells. A possible mechanism of action. Arzneimittelforschung 51:679–682

    CAS  PubMed  Google Scholar 

  • Hou XL, Kong Y, Wang ML, Yan AX (2015) QSAR Studies on the bioactivity of plasmodium falciparum glucose-6-phosphate dehydrogenase inhibitors. Lett Drug Des Discov 12:728–735

    Article  CAS  Google Scholar 

  • Jedhe GS, Paul D, Gonnade RG, Santra MK, Hamel E, Nguyen TL, Sanjayan GJ (2013) Correlation of hydrogen-bonding propensity and anticancer profile of tetrazole-tethered combretastatin analogues. Bioorg Med Chem Lett 23:4680–4684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Motohashi N, Wakabayashi H, Kurihara T, Fukushima H, Yamada T, Kawase M, Sohara Y, Tani S, Shirataki Y, Sakagami H, Satoh K, Nakashima H, Molnar A, Spengler G, Gyemant N, Ugocsai K, Molnar J (2004) Biological activity of barbados cherry (acerola fruits, fruit of Malpighia emarginata DC) extracts and fractions. Phytother Res 18:212–223

    Article  PubMed  Google Scholar 

  • Neighbors JD, Salnikova MS, Beutler JA, Wiemer DF (2006) Synthesis and structure-activity studies of schweinfurthin B analogs: evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity. Bioorg Med Chem 14:1771–1784

    Article  CAS  PubMed  Google Scholar 

  • Pradeep PS, Shrungesh Kumar TO, Prashantha N, Mahadevan KM (2015) Synthesis, in vitro antibacterial, toxicity and molecular docking anticancer activity of novel N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline Schiff Bases. Int J Curr Pharm Res 7:37–46

    CAS  Google Scholar 

  • Suleyman H, Gul HI, Gul M, Alkan M, Gocer F (2007) Anti-inflammatory activity of bis(3-aryl-3-oxo-propyl)methylamine hydrochloride in rat. Biol Pharm Bull 30:63–67

    Article  CAS  PubMed  Google Scholar 

  • Tugrak M, Gul HI, Sakagami H (2015a) Synthesis and cytotoxicities of 2-[4-hydroxy-(3,5-bis-aminomethyl)-benzylidene]-indan-1-ones. Lett Drug Des Discov 12:806–812

    Article  CAS  Google Scholar 

  • Tugrak M, Yamali C, Sakagami H, Gul HI (2015b) Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities. J Enzyme Inhib Med Chem 31(5):818–823

    Article  PubMed  Google Scholar 

  • Yerdelen KO, Gul HI, Sakagami H, Umemura N (2015a) Synthesis and biological evaluation of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one and its aminomethyl derivatives. J Enzyme Inhib Med Chem 30:383–388

    Article  CAS  PubMed  Google Scholar 

  • Yerdelen KO, Gul HI, Sakagami H, Umemura N, Sukuroglu M (2015b) Synthesis and cytotoxic activities of a curcumin analogue and its bis-Mannich derivatives. Lett Drug Des Discov 12:643–649

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research work was supported by Ataturk University Research Found (Project No. BAP: 2011/289, 2012/75), Turkey.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey

    Mehtap Tugrak & Halise Inci Gul

  2. School of Dentistry, Division of Pharmacology, Meikai University, Sakado, Saitama, Japan

    Hiroshi Sakagami

  3. Department of Organic Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey

    Ebru Mete

Authors
  1. Mehtap Tugrak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Halise Inci Gul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroshi Sakagami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ebru Mete
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Halise Inci Gul.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tugrak, M., Gul, H.I., Sakagami, H. et al. Synthesis and anticancer properties of mono Mannich bases containing vanillin moiety. Med Chem Res 26, 1528–1534 (2017). https://doi.org/10.1007/s00044-017-1833-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-017-1833-x

Keywords

Search

Navigation