Benchmark study of benzamide derivatives and four novel theoretically designed (L1, L2, L3, and L4) ligands and evaluation of their biological properties by DFT approaches

  • Amanullah
  • Usman AliEmail author
  • Muhammad Ans
  • Javed IqbalEmail author
  • Muhammad Adnan IqbalEmail author
  • Muhammad Shoaib
Original Paper


Four novel ligands, namely N-benzhydryl benzamide, N, N-diphenethyl benzamide, N, N-dihexyl benzamide, and N, N-dioctyl benzamide (L1, L2, L3, and L4, respectively), based on the benzamide unit were designed and computed for their different properties, such as absorption spectrum, dipole moment, theoretically expected biological properties, and frontier molecular orbitals, by evaluating the HOMO/LUMO energy orbitals strength with DFT approaches and comparing these properties with the R benzamide properties available in literature. All molecules have a suitable frontier molecular orbital diagram and L1 exhibits maximum absorption at 246.8 nm due to the strong electron donating effect of the diphenylmethane ligand group. Moreover, strongly extended conjugated groups caused a redshift in absorption spectra. Newly designed molecules may show strong biological activities against cancer, bacterial diseases, and harmful fungal disorders.

Graphical abstract

Orbital energy, electron density and frontier molecular orbitals view of four designed novel benzamide derivates


Density functional theory Frontier molecular orbitals Density of state Biological applications Proposed synthesis scheme 



The Computations/simulations/SIMILAR were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at Umeå University, 901 87, Umeå, Sweden. The authors acknowledge the financial and technical support from Punjab Bio-energy Institute (PBI), University of Agriculture Faisalabad (UAF). Dr. MAI is thankful to HEC-Pakistan for awarding research Project NRPU-8396.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

894_2019_4115_MOESM1_ESM.docx (29 kb)
ESM 1 (DOCX 28 kb)


  1. 1.
    Fujita K-i et al (2003) N-alkylation of amines with alcohols catalyzed by a Cp* Ir complex. Tetrahedron Lett 44(13):2687–2690CrossRefGoogle Scholar
  2. 2.
    Guillena G, Ramón DJ, Yus M (2009) Hydrogen autotransfer in the N-alkylation of amines and related compounds using alcohols and amines as electrophiles. Chem Rev 110(3):1611–1641CrossRefGoogle Scholar
  3. 3.
    Wetzel S et al (2011) Biology-oriented synthesis. Angew Chem Int Ed 50(46):10800–10826CrossRefGoogle Scholar
  4. 4.
    Zhu Z, Chen D (2002) Nitrogen fertilizer use in China–contributions to food production, impacts on the environment and best management strategies. Nutr Cycl Agroecosyst 63(2–3):117–127CrossRefGoogle Scholar
  5. 5.
    Weil RR, Brady NC, Weil RR (2016) The nature and properties of soils. Pearson, LondonGoogle Scholar
  6. 6.
    Lv W et al (2017) Synthesis of 2-Alkylaminoquinolines and 1, 8-Naphthyridines by successive ruthenium-catalyzed Dehydrogenative annulation and N-alkylation processes. Adv Synth Catal 359(7):1202–1207CrossRefGoogle Scholar
  7. 7.
    Bundrick W et al (2003) Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology 62(3):537–541CrossRefGoogle Scholar
  8. 8.
    Perkins JC, Devetski M, Dowling M Ampicillin in the treatmentGoogle Scholar
  9. 9.
    Yunus M, Rahman ASM, Faruque ASG, Glass RI (1981) A clinical trial of ampiciline versus trimethoprimsulfamethoxazole in the treatment of shigella dysentery. Dacca, ICDDRB; 1981Google Scholar
  10. 10.
    Pearson DC et al (1995) Azathioprine and 6-mercaptopurine in Crohn disease: a meta-analysis. Ann Intern Med 123(2):132–142CrossRefGoogle Scholar
  11. 11.
    Pearson D et al. (2000) Azathioprine for maintaining remission of Crohn's disease. Cochrane Database Syst Rev (2):CD000067–CD000067Google Scholar
  12. 12.
    Burghart A et al (1999) 3, 5-Diaryl-4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) dyes: synthesis, spectroscopic, electrochemical, and structural properties. J Org Chem 64(21):7813–7819CrossRefGoogle Scholar
  13. 13.
    Friedli F (2001) Detergency of specialty surfactants 98. CrossRefGoogle Scholar
  14. 14.
    Holmberg K (2003) Novel surfactants: preparation applications and biodegradability, revised and expanded 114. CRC, Boca RatonGoogle Scholar
  15. 15.
    Egan R (1978) Cationic surface active agents as fabric softeners. J Am Oil Chem Soc 55(1):118–121CrossRefGoogle Scholar
  16. 16.
    Yanai T, Tew DP, Handy NC (2004) A new hybrid exchange–correlation functional using the coulomb-attenuating method (CAM-B3LYP). Chem Phys Lett 393(1–3):51–57CrossRefGoogle Scholar
  17. 17.
    Mohan N et al (2010) Comparison of aromatic NH··· π, OH··· π, and CH··· π interactions of alanine using MP2, CCSD, and DFT methods. J Comput Chem 31(16):2874–2882PubMedGoogle Scholar
  18. 18.
    Chattaraj PK, Bhaumik S, Niser B Check of size consistency in different levels of theoryGoogle Scholar
  19. 19.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb M, Cheeseman JR et al (2009) Gaussian 09, revision D. 01. Gaussian, Inc., Wallingford, CTGoogle Scholar
  20. 20.
    Dennington RD, Keith TA, Millam JM (2008) GaussView 5.0. 8. Gaussian Inc, WallingfordGoogle Scholar
  21. 21.
    Civalleri B et al (2008) B3LYP augmented with an empirical dispersion term (B3LYP-D*) as applied to molecular crystals. Cryst Eng Comm 10(4):405–410CrossRefGoogle Scholar
  22. 22.
    Adamo C, Barone V (1998) Exchange functionals with improved long-range behavior and adiabatic connection methods without adjustable parameters: the m PW and m PW1PW models. J Chem Phys 108(2):664–675CrossRefGoogle Scholar
  23. 23.
    Chai J-D, Head-Gordon M (2008) Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections. Phys Chem Chem Phys 10(44):6615–6620CrossRefGoogle Scholar
  24. 24.
    Yu C, Hao X, Shen Q (2010) Illustration of origin 8.0. Chemical Industry Press, BeijingGoogle Scholar
  25. 25.
    Tenderholt AL (2006) PyMOlyze: a program to analyze quantum chemistry calculations, version 2.0.Google Scholar
  26. 26.
    Mariappan A, Das KM, Jeganmohan M (2018) Remote alkylation of N-(quinolin-8-yl) benzamides with alkyl bromides via ruthenium (ii)-catalyzed C–H bond activation. Org Biomolec Chem 16(18):3419–3427CrossRefGoogle Scholar
  27. 27.
    Srivastava SK, Chauhan PMS, Bhaduri AP (1999) A novel strategy for N-alkylation of primary amines. Synth Commun 29(12):2085–2091CrossRefGoogle Scholar
  28. 28.
    Daniel P et al. (2018) Palladium-catalyzed synthesis of α-trifluoromethyl benzylic amines via fluoroarylation of gem-difluoro-2-azadienes enabled by phosphine-catalyzed formation of an azaallyl–silver intermediate. ACS Catal 9(1):205–210CrossRefGoogle Scholar
  29. 29.
    Wolf M et al (2005) Alkylating benzamides with melanoma cytotoxicity: role of melanin, tyrosinase, intracellular pH and DNA interaction. Melanoma Res 15(5):383–391CrossRefGoogle Scholar
  30. 30.
    Han C et al (2004) Copper-mediated synthesis of N-acyl vinylogous carbamic acids and derivatives: synthesis of the antibiotic CJ-15,801. Org Lett 6(1):27–30CrossRefGoogle Scholar
  31. 31.
    Shalaby AA et al (2000) Synthesis and antifungal activity of some new quinazoline and benzoxazinone derivatives. Archiv der Pharmazie: Int J Pharmaceut Med Chem 333(11):365–372CrossRefGoogle Scholar
  32. 32.
    Muktapuram PR et al (2012) Anticancer siRNA delivery by new anticancer molecule: a novel combination strategy for cancer cell killing. Eur J Med Chem 56:400–408CrossRefGoogle Scholar
  33. 33.
    Abdizadeh T et al (2017) Design, synthesis and biological evaluation of novel coumarin-based benzamides as potent histone deacetylase inhibitors and anticancer agents. Eur J Med Chem 132:42–62CrossRefGoogle Scholar
  34. 34.
    Prajapati AK, Modi VP (2011) Synthesis and biological activity of n-{5-(4-methylphenyl) diazenyl-4-phenyl-1, 3-thiazol-2-yl} benzamide derivatives. Química Nova 34(5):771–774Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Agriculture FaisalabadFaisalabadPakistan
  2. 2.Punjab Bio-energy InstituteUniversity of AgricultureFaisalabadPakistan
  3. 3.Organometallic and Coordination Chemistry Laboratory, Department of ChemistryUniversity of AgricultureFaisalabadPakistan

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