Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Green Chemistry
  4. Volume 11, Issue 3
  5. Article
Volume 11, Issue 3
  • ISSN: 2213-3461
  • E-ISSN: 2213-347X

Abstract

Introduction

Many medicinally active new chemical entities depend on indole conjugated chromeno[d]pyrimidine derivatives as a building block. The synthesis of 4-(1H-indol-3-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione were achieved in the current study by treating 4-hydroxy-2H-chromen-2-one , indole aldehydes , and urea/thiourea in the presence of L-proline.

Methods

By adopting the above protocol, we were able to synthesize eight compounds, . 4-(1H-indol-3-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-diones (-), in the presence of L-proline as a catalyst in ethanol as solvent for 2-3 hours at 70-75°C with decent yields of 80-85%, and their structures were ascertained by various spectral techniques. They were further screened for their potentiality to inhibit cancer growth in HepG2 and MDA-MD-231 cells.

Results

The scope of the synthesis of biological relevant Indole conjugated Chromeno[d]Pyrimidines by three-component reaction (MCRs) process was investigated. The most optimised conditions obtained were 0.3 eq of L-proline for 2 hours at 70-75°C which gave the best yield (85%). The few advantages of this newly developed method are excellent yields, no metal catalyst, less toxic solvents, simple workup no chromatographic column purifications. On further screening for their anticancer activities, out of all, the compound displayed noteworthy cytotoxicity with IC values of 8.1 and 9.2 µM against HepG2 and MDA-MD-231, respectively. Additionally, studies also supported that compound had favourable binding energy (-7.8 kcal/mol) when compared to the co-crystal ligand (LS5) in inhibiting the human cyclin-dependent kinase 2 (CDK2) protein.

Conclusion

In conclusion, we have developed a simple, convenient, and efficient method for the synthesis of structurally diverse indole conjugated chromeno[d]pyrimidine analogues in the presence of L-proline as catalyst in ethanol as solvent with good yields. Further, the cytotoxic studies against HepG2 and MDA-MD-231 cells demonstrated that the synthesized compounds had good to reasonable activity, except for compound .

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cgc/10.2174/0122133461267868231018100148
2023-10-20
2025-01-19

  • From This Site

    /content/journals/cgc/10.2174/0122133461267868231018100148
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SinghP.K. SilakariO. The current status of O-heterocycles: A synthetic and medicinal overview.Chem Med Chem201813111071108710.1002/cmdc.20180011929603634
     [Google Scholar]
  2. AgarwalS. SethiyaA. SoniJ. SahibaN. TeliP. An overview of recent advances in the catalytic synthesis of substituted pyrans.Appl. Organomet. Chem.2022364e660410.1002/aoc.6604
     [Google Scholar]
  3. DamghaniF.K. KiyaniH. PourmousaviS.A. Green three-component synthesis of merocyanin dyes based on 4- arylideneisoxazol-5(4H)-ones.Curr. Green Chem.20207221722510.2174/2213346107666200122093906
     [Google Scholar]
  4. MaC. ZhouJ.Y. ZhangY.Z. JiaoY. MeiG.J. ShiF. Synergistic‐catalysis‐enabled reaction of 2‐indolymethanols with oxonium ylides for the construction of 3‐indolyl‐3‐alkoxy oxindole frameworks.Chem. Asian J.201813172549255810.1002/asia.20180062029791067
     [Google Scholar]
  5. DhavariaS. DhimanM. A facile one-pot four-component green synthesis of 4-(1H-Indol-2-yl)-4H-chromenes conjugated with phthalazine-1,4-diones.Russ. J. Org. Chem.202359472673210.1134/S1070428023040231
     [Google Scholar]
  6. BanerjeeB. KaurM. SharmaA. SinghA. PriyaA. GuptaV.K. JaitakV. Glycine catalyzed one-pot three-component synthesis of structurally diverse 2-amino substituted pyran annulated heterocycles in aqueous ethanol under refluxed conditions.Curr. Green Chem.20229316217310.2174/2213346110666221212152202
     [Google Scholar]
  7. ZiaraniG.M. NasabN.H. LashgariN. Synthesis of heterocyclic scaffolds through 6-aminouracil-involved multicomponent reactions.RSC Advances20166388273884810.1039/C6RA02834A
     [Google Scholar]
  8. KeriR.S. HosamaniK.M. ShingalapurR.V. HugarM.H. Analgesic, anti-pyretic and DNA cleavage studies of novel pyrimidine derivatives of coumarin moiety.Eur. J. Med. Chem.20104562597260510.1016/j.ejmech.2010.02.04820356657
     [Google Scholar]
  9. MahmoudN. M. Y. Abdel-RahmanB. A. E. AhmedA. F. MayA. E. NabilM. Y. Synthesis and cytotoxic evaluation of novel chromenes and chromene(2,3-d)pyrimidines.J Appl Pharm Sci20201012035043
     [Google Scholar]
  10. JavahershenasR. KhalafyJ. A new synthesis of pyrrolo[3,2- d]pyrimidine derivatives by a one-pot, three-component reaction in the presence of L-proline as an organocatalyst.Heterocycl. Commun.2018241374110.1515/hc‑2017‑0187
     [Google Scholar]
  11. MamaghaniaM. NiaR.H. TavakoliF. JahanshahiP. Recent advances in the MCRs synthesis of chromenes: A review.Curr. Org. Chem.20182216610.2174/138527282201180220105434
     [Google Scholar]
  12. BasumataryG. MohantaR. BezG. l-Proline derived secondary aminothiourea organocatalyst for synthesis of coumarin derived trisubstituted methanes: Rate enhancement by bifunctional catalyst over cooperative catalysis.Catal. Lett.2019149102776278610.1007/s10562‑019‑02809‑4
     [Google Scholar]
  13. BrahmachariG. MandalM. KarmakarI. NurjamalK. MandalB. ultrasound-promoted expedient and green synthesis of diversely functionalized 6-amino-5-((4-hydroxy-2-oxo-2 h -chromen-3-yl)(aryl)methyl)pyrimidine-2,4(1 H, 3 H)-diones via one-pot multicomponent reaction under sulfamic acid catalysis at ambient conditions.ACS Sustain. Chem.& Eng.2019766369638010.1021/acssuschemeng.9b00133
     [Google Scholar]
  14. AbdolmohammadiS. BalalaieS. BarariM. RomingerF. Three-component green reaction of arylaldehydes, 6-amino-1,3- dimethyluracil and active methylene compounds catalyzed by Zr(HSO4)4 under solvent-free conditions.Comb. Chem. High Throughput Screen.201316215015923092170
     [Google Scholar]
  15. BhartiR. ParvinT. Molecular diversity from the l-proline-catalyzed, three-component reactions of 4-hydroxycoumarin, aldehyde, and 3-aminopyrazole or 1,3-dimethyl-6-aminouracil.Synth. Commun.201545121442145010.1080/00397911.2015.1023900
     [Google Scholar]
  16. BhartiR. ParvinT. Diversity oriented synthesis of tri-substituted methane containing aminouracil and hydroxynaphthoquinone/hydroxycoumarin moiety using organocatalysed multicomponent reactions in aqueous medium.RSC Advances2015582668336683910.1039/C5RA13093J
     [Google Scholar]
  17. PratapR. RamV.J. Natural and synthetic chromenes, fused chromenes, and versatility of dihydrobenzo[h]chromenes in organic synthesis.Chem. Rev.201411420104761052610.1021/cr500075s25303539
     [Google Scholar]
  18. EllisG.P. WeissbergerA. TaylorE.C. Chromenes, Chromanones and Chromones.John WileyNew York1977211139
     [Google Scholar]
  19. HafezE.A.A. ElnagdiM.H. ElagameyA.G.A. El-TaweelF.M.A.A. Nitriles in heterocyclic synthesis: novel synthesis of benzo[c]coumarin and of benzo[c]pyrano[3, 2-c]quinoline derivatives.Heterocycles19872690390710.3987/R‑1987‑04‑0903
     [Google Scholar]
  20. ThomasN. ZachariahS.M. Pharmacological activities of chromene derivatives: An overview.Asian J. Pharm. Clin. Res.2013621115
     [Google Scholar]
  21. Ying-JenC. Shih-MingH. Ming-ChengT. Jiann-TorngC. An-RongL. Ren-YeongH. Chang-MinL. The anti-fibrotic and anti-inflammatory effects of 2,4-diamino-5-(1-hydroxynaphthalen-2-yl)-5H-chromeno[2,3-b] pyriine-3-carbonitrile in corneal fibroblasts.Pharmacol. Rep.20207211512510.1007/s43440‑019‑00026‑932016832
     [Google Scholar]
  22. HuffordC.D. OguntimeinB.O. Van EngenD. MuthardD. ClardyJ. Vafzelin and uvafzelin, novel constituents of Uvaria afzelii.J. Am. Chem. Soc.1980102247365736710.1021/ja00544a037
     [Google Scholar]
  23. FuendjiepV. NkengfackA.E. FomumZ.T. SondengamB.L. BodoB. Conrauinones A and B, two new isoflavones from stem bark of Millettia conraui.J. Nat. Prod.199861338038310.1021/np970187g9548880
     [Google Scholar]
  24. Jean WJ. FomumZ.T. TillequinF. LibotF. KochM. Erysenegalenseins B and C, two new prenylated isoflavanones from Erythrina senegalensisJ. Nat. Prod.199558105108
     [Google Scholar]
  25. AbdolmohammadiS. MirzaB. VessallyE. Immobilized TiO2 nanoparticles on carbon nanotubes: an efficient heterogeneous catalyst for the synthesis of chromeno[b]pyridine derivatives under ultrasonic irradiation.RSC Advances2019971418684187610.1039/C9RA09031B35557875
     [Google Scholar]
  26. MotamediR. Synthesis of novel chromeno[4′,3′- b]pyrano[6,5-b]quinoline derivatives.Heterocycl. Commun.2011175-616917210.1515/HC.2011.047
     [Google Scholar]
  27. KumarU.T. BobdeY. SravaniP. RanganK. GhoshB. BhattacharyaA. Fused chromeno‐thieno/furo‐pyridines as potential analogs of lamellarin d and their anticancer activity evaluation.ChemistrySelect20194107261073010.1002/slct.201902946
     [Google Scholar]
  28. Oliveira-PintoaS. LudovicoaP. CostaM. Unravelling the anticancer potential of functionalized chromeno[2,3-b]pyridines for breast cancer treatment.Bioorg. Chem.202010010394210.1016/j.bioorg.2020.103942
     [Google Scholar]
  29. SarkarN. SinghA. KumarP. KaushikM. Protein kinases: Role of their dysregulation in carcinogenesis, identification and inhibition.Drug Res. (Stuttg.)202373418919910.1055/a‑1989‑185636822216
     [Google Scholar]
  30. BorgoC. RuzzenM. Role of protein kinase CK2 in antitumor drug resistance.J. Exp. Clin. Cancer Res.20193828710.1186/s13046‑019‑1292‑y31277672
     [Google Scholar]
  31. ChenY. WangY. WangJ. ZhouZ. CaoS. ZhangJ. Strategies of targeting CK2 in drug discovery: Challenges, opportunities, and emerging prospects.J. Med. Chem.20236642257228110.1021/acs.jmedchem.2c0152336745746
     [Google Scholar]
  32. MosmannT. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.J. Immunol. Methods1983651-2556310.1016/0022‑1759(83)90303‑46606682
     [Google Scholar]
  33. WanM. ZhangL. ChenY. LiQ. FanW. XueQ. YanF. SongW. Synthesis and anticancer activity evaluation of novel phenanthridine derivatives.Front. Oncol.2019927410.3389/fonc.2019.0027431058081
     [Google Scholar]
  34. Ghanbari-ArdestaniS. Khojasteh-BandS. ZaboliM. HassaniZ. MortezaviM. MahaniM. Torkzadeh-MahaniM. The effect of different percentages of triethanolammonium butyrate ionic liquid on the structure and activity of urate oxidase: Molecular docking, molecular dynamics simulation, and experimental study.J. Mol. Liq.201929211131810.1016/j.molliq.2019.111318
     [Google Scholar]
  35. WallaceA.C. LaskowskiR.A. ThorntonJ.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions.Protein Eng. Des. Sel.19958212713410.1093/protein/8.2.127
     [Google Scholar]
/content/journals/cgc/10.2174/0122133461267868231018100148
Loading
Eco-friendly Synthesis of Indole Conjugated Chromeno[d]Pyrimidines as Anti-cancer Agents and their Molecular Modelling Studies
Curr Green Chem 11, 221 (2024); https://doi.org/10.2174/0122133461267868231018100148
/content/journals/cgc/10.2174/0122133461267868231018100148
/content/journals/cgc/10.2174/0122133461267868231018100148
Loading

Data & Media loading...

Supplements

file format download Download

  • Article Type:     Letter
Keyword(s): anti-cancer activity; Eco-friendly; green synthesis; indole conjugated chromeno[d]pyrimidines; L-proline; molecular descriptors prediction

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test