Synthesis, Characterization, ADME Study and Antimicrobial Evaluation of New 1,2,3-triazole Derivatives of 2-phenyl benzimidazole.

Asmaa Adnan Abdulnabi; Karima Fadhil Ali; Basma M.Abd Razik

doi:10.32947/ajps.v23i2.1016

Authors

Asmaa Adnan Abdulnabi Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Karima Fadhil Ali Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Basma M.Abd Razik Department of Pharmaceutical Chemistry, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.32947/ajps.v23i2.1016

Keywords:

azide, amide, 1,2,3-triazole, acetylene derivatives, ADME.

Abstract

Novel 2-amino benzimidazole derivatives containing amide, azide and 1,2,3-triazole moieties have been synthesized. Compound 3 was synthesized by reaction of o-phenylenediamine with p-aminobenzoic acid. Compound 3 was converted into amide by treatment with chloroacetyl chloride to get compound 4. Compound 4 and sodium azide were combined to create compound which has an azide group. Compound 5 was converted into 1,2,3-triazole derivatives by treatment with acetylene derivatives. FTIR, ¹H-NMR, and Mass spectra have been used to confirm the chemical structures of various substances. By using a technique called well diffusion agar, the final products were examined in vitro to predict activity against two kinds of gram-positive bacteria and two kinds of gram-negative bacteria as well as the antifungal activity against Candida albicans fungus. All the final products exhibited moderate to potent activity compared to Trimethoprim and Fluconazole as reference antibacterial and antifungal drugs respectively. Swiss ADME was also used to undertake ADME tests to determine the bioavailability, drug-likeness and topological polar surface area of the synthesized molecule. The results showed that every chemical tested was absorbed orally and followed the Lipinski rule.

References

Alboofetileh M, Rezaei M, Hosseini H, Abdollahi M. Antimicrobial activity of alginate/clay nanocomposite films enriched with essential oils against three common foodborne pathogens. Food Control. 2014;36(1):1–7.

Taha DE, Raauf AMR, Ali KF. Design, Synthesis, Characterization, Biological Activity and ADME Study of New 5-arylidene-4-Thiazolidinones Derivatives Having. Al Mustansiriyah J Pharm Sci. 2019;19(4):77–88.

Konda S, Raparthi S, Bhaskar K, Munaganti RK, Guguloth V, Nagarapu L, et al. Synthesis and antimicrobial activity of novel benzoxazine sulfonamide derivatives. Bioorg Med Chem Lett. 2015;25(7):1643–6.

Hashem HE, El Bakri Y. An overview on novel synthetic approaches and medicinal applications of benzimidazole compounds. Arab J Chem. 2021;14(11):103418.

Khan AK. Facile Synthesis, Characterization of New Quinazolinones with Different Azo Compounds, 1, 2, 3-Triazole Moieties and Evaluation Their Anti-bacterial Activity. Al-Mustansiriyah J Sci. 2017;28(3):122–33.

Dixit D, Verma PK, Marwaha RK. A review on ‘triazoles’: their chemistry, synthesis and pharmacological potentials. J Iran Chem Soc. 2021;18(10):2535–65.

Al-Smaisim RF, Sharba AHK, Al-Bayati RI. Synthesis of 1, 2, 3-Triazole Compounds Derived from 4-Amino Benzoic Acid. Al-Mustansiriyah J Sci. 2010;21(5).

Massarotti A, Aprile S, Mercalli V, Del Grosso E, Grosa G, Sorba G, et al. Are 1, 4‐and 1, 5‐Disubstituted 1, 2, 3‐Triazoles Good Pharmacophoric Groups? ChemMedChem. 2014;9(11):2497–508.

Agalave SG, Maujan SR, Pore VS. Click chemistry: 1, 2, 3‐triazoles as pharmacophores. Chem Asian J. 2011;6(10):2696–718.

Bonandi E, Christodoulou MS, Fumagalli G, Perdicchia D, Rastelli G, Passarella D. The 1, 2, 3-triazole ring as a bioisostere in medicinal chemistry. Drug Discov Today. 2017;22(10):1572–81.

Carvalho da Silva F de, Cardoso MF do C, Ferreira PG, Ferreira VF. Biological Properties of 1H-1, 2, 3-and 2H-1, 2, 3-Triazoles. Chem 1, 2, 3-triazoles. 2014;117–65.

Bi F, Ji S, Venter H, Liu J, Semple SJ, Ma S. Substitution of terminal amide with 1H-1, 2, 3-triazole: Identification of unexpected class of potent antibacterial agents. Bioorg Med Chem Lett. 2018;28(5):884–91.

Lakkakula R, Roy A, Mukkanti K, Sridhar G. Synthesis and anticancer activity of 1, 2, 3-triazole fused N-arylpyrazole derivatives. Russ J Gen Chem. 2019;89(4):831–5.

Angajala KK, Vianala S, Macha R, Raghavender M, Thupurani MK, Pathi PJ. Synthesis, anti-inflammatory, bactericidal activities and docking studies of novel 1, 2, 3-triazoles derived from ibuprofen using click chemistry. Springerplus. 2016;5(1):1–15.

Guo H-Y, Chen Z-A, Shen Q-K, Quan Z-S. Application of triazoles in the structural modification of natural products. J Enzyme Inhib Med Chem. 2021;36(1):1115–44.

Kolb HC, Finn MG, Sharpless KB. Click chemistry in glycoscience: new developments and strategies. Angew Chem Int Ed. 2001;40(11):2004–21.

Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chemie Int Ed. 2001;40(11):2004–21.

Harkala KJ, Eppakayala L, Maringanti TC. Synthesis and biological evaluation of benzimidazole-linked 1, 2, 3-triazole congeners as agents. Org Med Chem Lett. 2014;4(1):1–4.

Khattab M, Galal SA, Ragab FAF, El Diwani HI. Different synthetic routes to 4-(1H-benzo [d] imidazol-2-yl) aniline. Res Chem Intermed. 2013;39(7):2917–23.

Kuntala N, Telu JR, Banothu V, Nallapati SB, Anireddy JS, Pal S. Novel benzoxepine-1, 2, 3-triazole hybrids: synthesis and pharmacological evaluation as potential antibacterial and anticancer agents. Medchemcomm. 2015;6(9):1612–9.

Al-Blewi FF, Almehmadi MA, Aouad MR, Bardaweel SK, Sahu PK, Messali M, et al. Design, synthesis, ADME prediction and pharmacological evaluation of novel benzimidazole-1, 2, 3-triazole-sulfonamide hybrids as antimicrobial and antiproliferative agents. Chem Cent J. 2018;12(1):1–14.

Daina A, Zoete V. A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 2016;11(11):1117–21.

Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016;6(2):71–9.

Palm K, Stenberg P, Luthman K, Artursson P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res. 1997;14(5):568–71.