Skip to main content

Advertisement

Log in

Synthesis, spectral analysis, DFT calculations, biological potential and molecular docking studies of indole appended pyrazolo-triazine

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A series of novel 5-(3,5-disubstituted-1H-indol-2-yl)-2,3-dimethyl-1-phenyl-2,6-dihydro-1H-pyrazolo[4,3-e][1,2,4]triazines (3a-l) were synthesized in single step from 3,5-disubstituted indole-2-carbohydrazide and 4-aminoantipyrine under acidic conditions with excellent yields. The various spectroscopic methods were used to prove the formation of all these products. The compounds 3a, 3b, 3e, 3f, 3i and 3j exhibited excellent antibacterial and antifungal activities with an MIC value of 3.125 µg/ml against the tested pathogens and anti-tuberculosis inhibitory potential against M. tuberculosis which is equivalent to standard drug. The antidiabetic activity of the compounds 3a and 3b showed the maximum potential as glucosidase inhibitors with IC50 = 47.21 μg/ml and IC50 = 48.36 μg/ml, respectively. The physicochemical characteristics like ADMET, drug-likeness and bioactivity scores for these molecules were also disclosed. To comprehend the electronic behavior of compound 3a, density functional theory estimations at the DFT/B3LYP level via 6-31G++ (d, p) have been carried out to replicate the structure and geometry. The first-order hyperpolarizability calculation was used to calculate the nonlinear visual feature of compound 3a. The charge transfer interface among the structure is elucidated by the estimated HOMO–LUMO analysis. Further, molecular docking studies were carried out for synthesized compounds with human maltase-glucoamylase (PDB: 2QMJ).

Graphical abstract

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Acharya PT, Jethava DJ, Vasava MS, Bhavsar ZA et al (2020) Synthesis, docking study and biological evaluation of novel N-(1,3-benzothiazole-2-yl)-2-(pyridine-3-ylformohydrazido) acetamide derivatives. Indian J Chem 59:1721–1737

    Google Scholar 

  2. Dorothée B, Mohamed K, Wim S, Gunter C et al (2018) Discovery of indole derivatives as novel and potent dengue virus inhibitors. J Med Chem 61(18):8390–8401. https://doi.org/10.1021/acs.jmedchem.8b00913

    Article  CAS  Google Scholar 

  3. Hawash M, Kahraman DC, Ergun SG et al (2021) Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines. BMC Chem 15:66–74. https://doi.org/10.1186/s13065-021-00793-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Basavarajaiah SM, Mruthyunjayaswamy BHM (2009) Synthesis and antimicrobial activity of some 5-substituted-3-phenyl-Nβ-(substituted-2-oxo-2H-pyrano[2,3-b]quinoline-3-carbonyl)-1H-indole-2-carboxyhydrazide. Chem Pharm Bull 57(6):557–560. https://doi.org/10.1248/cpb.57.557

    Article  Google Scholar 

  5. Che Z, Tian Y, Liu S, Hu M, Chen G (2018) Synthesis and in vitro anti-HIV-1 evaluation of some N-arylsulfonyl-3-formylindoles. Braz J Pharm Sci 54(3):e17044. https://doi.org/10.1590/s2175-97902018000317044

    Article  CAS  Google Scholar 

  6. Basavarajaiah SM, Mruthyunjayaswamy BHM (2018) Synthesis and antimicrobial activity of some 5-chloro-3-phenyl-1H-indole-2-carbonyl azide derivatives. Indian J Chem 57(03):390–399

    Google Scholar 

  7. Basavarajaiah SM, Mruthyunjayaswamy BHM (2016) Synthesis and antimicrobial activity of novel 5-substituted-N-(substituted-2H-[1,3]oxazino[6,5-b]quinolin-3(4H)-yl)-3-phenyl-1H-indole-2-carboxamides. Indian J Chem 55B(12):1115–1119

    Google Scholar 

  8. Basavarajaiah SM, Mruthyunjayaswamy BHM (2009) Synthesis and anti-microbial activity of some new 5-substituted-n1-[(1e)-(2-hydroxyquinolin-3-yl)methylene]-3-phenyl-1h-indole-2-carbohydrzide derivatives. Hetero Commun 15(3):217–224. https://doi.org/10.1515/HC.2009.15.3.217

    Article  CAS  Google Scholar 

  9. Mruthyunjayaswamy BHM, Shanthaveerappa BK, Basavarajaiah SM (2010) Synthesis and antimicrobial activity of 5-substituted-2-phenyl-3-(o-carboethoxyphenyl) iminomethyl indoles and their derivatives. J Indian Chem Soc 87(9):1109–1115. https://doi.org/10.1002/chin.201111132

    Article  CAS  Google Scholar 

  10. Yernale NG, Matada BS, Vibhutimath GB, Biradar VD, Karekal M, Udayagiri MD, Mruthyunjayaswamy BHM (2022) Indole core-based Copper(II), Cobalt(II), Nickel(II) and Zinc(II) complexes: synthesis, spectral and biological study. J Mol Struct 1248:131410. https://doi.org/10.1016/j.molstruc.2021.131410

    Article  CAS  Google Scholar 

  11. Jasiewicz B, Kozanecka-Okupnik W, Przygodzki M et al (2021) Synthesis, antioxidant and cytoprotective activity evaluation of C-3 substituted indole derivatives. Sci Rep 11:15425. https://doi.org/10.1038/s41598-021-94904-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sheshandrakumar KN, Sudharshan NR, Lokesh B, Basavarajaiah SM (2018) Design, synthesis and evaluation of antimicrobial activity of some novel 3- (4-substituted phenyl)-2-(2-substituted1h-indol-3-yl)-3, 4-dihydroimidazo [4, 5-b] indoles. Int J Creat Res Thoughts 6(2):2320–2328

    Google Scholar 

  13. Basavarajaiah SM, Mruthyunjayaswamya BHM (2021) Pharmacological activities of some 5-substituted-3-phenyl-Nβ-(substituted-2-oxo-2H-pyrano [2, 3-b] quinoline-3-carbonyl)-1H-indole-2-carboxyhydrazides. Der Pharmacia Sinica 12(5):011. https://doi.org/10.1248/cpb.57.557

    Article  CAS  Google Scholar 

  14. Imran A, Sofi DM, Ming Fa H, Zeid AA, Abdulrahman A (2018) Facile synthesis of indole heterocyclic compounds based micellar nano anti-cancer drugs. RSC Adv 8:37905–37914. https://doi.org/10.1039/C8RA07060A

    Article  Google Scholar 

  15. Nayak A, Saxena H, Bathula C et al (2021) Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum. Malar J 20:100–106. https://doi.org/10.1186/s12936-021-03632-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nalini R, Basavarajaiah SM, Nagesh GY, Ramakrishna Reddy K (2022) Design, synthesis and biological evaluation of novel isoniazid hybrids. J Indian Chem Soc 99(1):100273. https://doi.org/10.1016/j.jics.2021.100273

    Article  CAS  Google Scholar 

  17. Qinyuan Xu, Huang Li, Liu J, Ma L, Chen T et al (2012) Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes. Eur J Med Chem 52:70–81. https://doi.org/10.1016/j.ejmech.2012.03.006

    Article  CAS  Google Scholar 

  18. Basavarajaiah SM, Mruthyunjayaswamy BHM (2018) Synthesis and anti-microbial activity of (Z)-4-(4-substituted-thiazol-2-yl)-l-(2-oxoindolin-3-ylidene) semicarbazide and its derivatives. Indian J Chem 48B(10):1274–1278

    Google Scholar 

  19. Sheshandrakumar KN, Srividya J, Narayanaswamy BJ, Umesha K, Basavarajaiah SM (2017) Synthesis and evaluation of biological activity of some new 3, 7-substituted-2H-pyrano/thiopyrano[2, 3-b] quinolin-2-ones. Indian J Heteero Chem 27(3):281–288

    CAS  Google Scholar 

  20. Ansari A, Ali A, Asif M (2017) Review: biologically active pyrazole derivatives. New J Chem 41:16–41. https://doi.org/10.1039/C6NJ03181A

    Article  CAS  Google Scholar 

  21. Faisal M, Saeed A, Hussain S et al (2019) Recent developments in synthetic chemistry and biological activities of pyrazole derivatives. J Chem Sci 131:70–76. https://doi.org/10.1007/s12039-019-1646-1

    Article  CAS  Google Scholar 

  22. Raghu MS, Pradeep Kumar B, Prashanth MK, Yogesh Kumar K, Prathibha BS et al (2021) Novel 1,3,5-triazine-based pyrazole derivatives as potential antitumor agents and EFGR kinase inhibitors: synthesis, cytotoxicity, DNA binding, molecular docking and DFT studies. New J Chem 45:13909–13924. https://doi.org/10.1039/D1NJ02419A

    Article  CAS  Google Scholar 

  23. Singh S, Utreja D, Kumar V (2022) Pyrrolo[2,1-f][1,2,4]triazine: a promising fused heterocycle to target kinases in cancer therapy. Med Chem Res 31:1–25. https://doi.org/10.1007/s00044-021-02819-1

    Article  CAS  PubMed  Google Scholar 

  24. Matada BS, Pattanashettar R, Yernale NG (2021) A comprehensive review on the biological interest of quinoline and its derivatives. Bioorg Med Chem 32:115973. https://doi.org/10.1016/j.bmc.2020.115973

    Article  CAS  PubMed  Google Scholar 

  25. Matada BS, Yernale NG (2021) The contemporary synthetic recipes to access versatile quinoline heterocycles. Synth Commun 51:1133–1159. https://doi.org/10.1080/00397911.2021.1876240

    Article  CAS  Google Scholar 

  26. Matada BS, Yernale NG (2021) Modern encroachment in synthetic approaches to access nifty quinoline heterocycles. J Indian Chem Soc 98:100174. https://doi.org/10.1016/j.jics.2021.100174

    Article  CAS  Google Scholar 

  27. Mathada BS, Yernale NG, Basha NJ, Badiger J (2021) An insight into the advanced synthetic recipes to access ubiquitous indole heterocycles. Tetrahedron Lett 85:153458. https://doi.org/10.1016/j.tetlet.2021.153458

    Article  CAS  Google Scholar 

  28. Matada BS, Yernale NG, Javeed M (2021) Design, spectroscopic studies, DFT calculations and evaluation of biological activity of novel 1,3-benzoxazines encompassing isoniazid. Polycycl Aromat Compd. https://doi.org/10.1080/10406638.2021.2019062

    Article  Google Scholar 

  29. Basavarajaiah SM, Nagesh GY, Basha NJ (2021) Updates on the versatile quinoline heterocycles as anticancer agents. Phys Sci Rev. https://doi.org/10.1515/psr-2021-0040

    Article  Google Scholar 

  30. Jeelan Basha N, Basavarajaiah SM, Shyamsunder K (2022) Therapeutic potential of pyrrole and pyrrolidine analogs: an update. Mol Divers. https://doi.org/10.1007/s11030-022-10387-8

    Article  PubMed  PubMed Central  Google Scholar 

  31. Jeelan Basha N, Basavarajaiah SM, Swathi B, Kumar P (2021) A comprehensive insight on the biological potential of embelin and its derivatives. Nat Prod Res. https://doi.org/10.1080/14786419.2021.1955361

    Article  PubMed  Google Scholar 

  32. Nalini R, Basavarajaiah SM, Nagesh GY, Ramakrishna Reddy K (2022) Synthesis, characterization and biological activity of ONO donor schiff base and its metal complexes. Asian J Chem 34(2):389–394

    Article  CAS  Google Scholar 

  33. Basavarajaiah SM, Sasidhar BS (2022) An insight into the recent developments in anti-infective potential of indole and associated hybrids. J Mol Struct. https://doi.org/10.1016/j.molstruc.2022.132808

    Article  Google Scholar 

  34. Nagesh GY, Mohammad J, Jeelan NB, Prashantha K, Nithin R et al (2022) Design, spectral analysis, DFT calculations, antimicrobial, Anti-TB, antioxidant activity and molecular docking studies of novel bis-benzoxazines with cytochrome c peroxidase. J Mol Struct. https://doi.org/10.1016/j.molstruc.2022.132808

    Article  Google Scholar 

  35. Rajashekara J, Shanthaveerappa BK, Angadi SD, Kulkarani VH, Mruthyunjayaswamy BHM (1998) Synthesis and biological activities indole derived metal complexes. Asian J Chem 10(2):306–311

    Google Scholar 

  36. Xiong G, Wu Z, Yi J, Li F, Yang Z (2021) ADMETlab 20: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res 49(W1):W5–W14. https://doi.org/10.1093/nar/gkab255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Parr RG, Yang W (1984) Density functional approach to the frontier-electron theory of chemical reactivity. J Am Chem Soc 106:4049–4050. https://doi.org/10.1021/ja00326a036

    Article  CAS  Google Scholar 

  38. Jawaher KR, Indirajith R, Krishnan S, Robert R, Das SJ (2018) Quantum chemical calculations of $$ hbox Cr}_{2 hbox {O}_{3}/ hbox {SnO}_{2}$$ Cr2O3/SnO2 using density functional theory method. Pramana-J Phys 90:38–42. https://doi.org/10.1007/s12043-018-1526-0

    Article  CAS  Google Scholar 

  39. Clinical and Laboratory Standards Institute (CLSI) (2015) Performance standards for antimicrobial disk susceptibility tests, 12th edn. CLSI Document M02-A12, CLSI, Wayne

    Google Scholar 

  40. Clinical and Laboratory Standards Institute (CLSI) (2015) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. CLSI Document M07-A10, CLSI, Wayne

    Google Scholar 

  41. Clinical and Laboratory Standards Institute (2008) Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard third edition; CLSI document M27–A3. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  42. Cihan-Üstündağ G, Şatana D, Özhan G, Çapan G (2016) Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents. J Enzyme Inhib Med Chem 31(3):369–380. https://doi.org/10.3109/14756366.2015.1024673

    Article  CAS  PubMed  Google Scholar 

  43. Kim YM, Wang MH, Rhee HI (2004) A novel alpha-glucosidase inhibitor from pine bark. Carbohydr Res 339(3):715–717. https://doi.org/10.1016/j.carres.2003.11.005

    Article  CAS  PubMed  Google Scholar 

  44. Ramesh SG, Avinash KK, Karabasanagouda T, Raghuveer SB, Mujawar H et al (2021) Synthesis of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives as potential glucosidase inhibitors. Bioorg Chem 114:105046. https://doi.org/10.1016/j.bioorg.2021.105046

    Article  CAS  Google Scholar 

  45. Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity: a rapid access to atomic charges. Tetrahedron 36(22):3219–3228. https://doi.org/10.1016/0040-4020(80)80168-2

    Article  CAS  Google Scholar 

  46. Sybyl-X 2.0 (2012) Tripos International, St. Louis

Download references

Acknowledgements

The authors are grateful to The Directors of IISc, Bengaluru, SAIF Punjab University, and CDRI, Lucknow, for spectral data. For biological activities, the authors are grateful to The Director, Skanda Life Sciences Pvt. Ltd., Bengaluru-560 091. Thanks are due to The Principal, Vijaya College, Bengaluru-560 004 and The Principal, Guru Nanak First Grade College, Bidar—585 403, for providing laboratory facilities to the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. M. Basavarajaiah.

Ethics declarations

Conflict of interest

The authors report no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 167 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Basavarajaiah, S.M., Nagesh, G.Y., Javeed, M. et al. Synthesis, spectral analysis, DFT calculations, biological potential and molecular docking studies of indole appended pyrazolo-triazine. Mol Divers 27, 679–693 (2023). https://doi.org/10.1007/s11030-022-10448-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-022-10448-y

Keywords

Navigation