AN EFFICIENT SYNTHESIS, CHARACTERIZATION AND BIOACTIVITY OF BENZIMIDA-ZOLE LINKED TRIAZOLES
HTML Full TextAN EFFICIENT SYNTHESIS, CHARACTERIZATION AND BIOACTIVITY OF BENZIMIDA-ZOLE LINKED TRIAZOLES
Asghar Jafar Khan and Abdul Rahim Abdul Sami *
Department of Chemistry, Milliya Arts, Scince & Mangement Science College, Beed, Maharashtra, India.
ABSTRACT: A series of benzimidazole-linked triazoles hybrids (4a-4u) have been synthesized by simple cyclization, followed by amide coupling and click reaction starting from o-phenylene diamines as substrates with 4-formylbenzioc acid, propargylamine and followed by treatment with aryl azides. The structure of synthesized compounds (4a-4u) was confirmed by spectral techniques. The prepared compounds were screened by the agar well diffusion method against both Gram-positive bacteria (S. aureus, B. subtilis, M. luteus and B. megatherium) as well as Gram-negative bacteria (E. coli, K. pneumoniae, S. typhi and S. paratyphi). Analysis of antibacterial activity profile of synthesized compounds revealed that compounds (4a) and (4c) exhibited prominent activity against all tested Gram positive and Gram-negative microbes.
Keywords: Triazoles, Benzimidazoles, Biological activity
INTRODUCTION: Since last decade there is considerable interest in the development of novel hybrid drug like molecules that include two pharmacophores in a single molecule in order to improve the efficacy of such compounds 1, 2. Benzimidazole which is a privileged heterocycle, attached to other heterocyclic moieties including fused rings resulted in compounds to give hybrid compound with enhanced pharmacological profile. Wonderful demands for novel bioactive molecules are continuously growing in the market 3. In the present scenario, development of better drugs in shorter times have always been challenge for medicinal chemists. However, synthesis of new molecules, combining high activity, drug likeness and good pharmacokinetic properties is equally fascinating 4.
There are two types of triazoles viz. 1,2,3 triazoles and 1,2,4 triazoles. 1,2,3-Triazole moieties are attractive one because of their high stability, tendency to form hydrogen bonding up surges their solubility which favour binding towards biomolecular targets in the cell 5-9. Its structural simplicity, ease of synthesis and pohavet cytotoxic properties in low nanomolar range has made it greatly pursued scaffold for the development of antimicrobial agents, some of the potent hybrid molecules that have been recently developed as new antibacterial agents were obtained by the combination of different pharmacophores 10-19. The promising biological activity exhibited by these hybrid molecules 20-22 prompted us to develop some newer hybrid molecules by linking the triazole pharmacophore with benzimidazole scaffold with a view to enhance their antimicrobial activity 23-25. Thus, a series of novel class of triazole-benzimidazole hybrids (4a–4u) has been synthesized and evaluated for their antimicrobial activity.
MATERIALS AND METHODS: O-Phenylenediamines, 4-formylbenzoic acid, propargylamine, aryl azides, and all solvents were procured from commercially available sources and used without further purification. Standard microbiological media were used for antibacterial activity assays.
Synthesis of Benzimidazole-Linked Triazole Hybrids (4a-4u): The compounds were synthesized through a multi-step process.
Cyclization: o-Phenylenediamines were reacted with 4-formylbenzoic acid under suitable conditions to form benzimidazole intermediates.
Amide Coupling: The benzimidazole intermediates were coupled with propargylamine to yield propargylated benzimidazole derivatives.
Click Reaction: The propargylated derivatives were treated with aryl azides under click chemistry conditions to obtain the final benzimidazole-linked triazole hybrids (4a-4u).
Antibacterial Activity Screening: The synthesized compounds (4a-4u) were evaluated for their antibacterial activity using the agar well diffusion method.
RESULT AND DISCUSSION: A series of benzimidazole linked triazole hybrids (4a-4u) were prepared by following the conventional synthetic procedures (Scheme 1). A condensation reaction between different o-phenylenediamine and 4-formylbenzioc acidgive rise benzimidazole linked carboxylic acids (2a-2u) which on coupling with propargylamine in presence of EDCI/HOBT furnished the terminal alkynes (3a-3d).
The final compounds (4a-4u) were prepared by a simple click reaction between these terminal alkynes (3a-3d) and aromatic azides. Structures of the final compounds were confirmed from their spectral data.
SCHEME 1: CONVENTIONAL SYNTHETIC PROCEDURES
Where R1 = H, Cl and Me; R2= H and Me; R3= Ph; R4; R5, R6 and R7 can be H, MeO, Ph, Cl and CF3
Reagent and Conditions: (a) 4-formylbenzioc acid, MeOH, 60 oC, 2-3 hr. (b) Propargylamine, EDCI, HOBt, DMF, at 0oC to r.t (c) Aryl Azides, CuSO4.5H20, Sodium ascorbate, tBuOH: H2O (1:1), rt, 3-4 hr.
SYNTHESISED BENZIMIDAZOLE LINKED TRIAZOLES
Experimental Section: All Chemicals used in this work were purchased from Aldrich and Merck chemical companies and used without purification. Reactions were monitored by TLC, performed on silica gel glass plates containing 60 F-254, and visualization on TLC was achieved by UV light or iodine indicator. Column chromatography was performed with Merck 60–120 mesh silica gel. 1H and 13C NMR spectra were recorded on Gemini Varian-VXR-unity (200, 400, 500 MHz) or Bruker UXNMR/XWIN-NMR (300 MHz) instruments. Chemical shifts (δ) are expressed in ppm relative to internal standard TMS. Multiplicities of NMR signals are represented as singlet (s), doublet (d), doublet of doublet (dd), triplet (t), quartet (q) and multiplet (m). ESI spectra were recorded on Micro mass, Quattro LC using ESI+ software with capillary voltage 3.98 kV and ESI mode positive ion trap detector.
General Procedure for the Synthesis of Benzimidazoles Acids (2a-2d): O-phenylenediamines (1a-1d) (0.025 mol) and 4-formyl benzoic acid (0.025 mol) in 100ml methanol was stirred at 60 oC for 2-3 hr. Completion of reaction was monitored by TLC. After completion, reaction cool down to room temperature then solid observed. It was filtered and washed with hexane. Yield: 83%, white solid (2a-2d).
4-(1H-benzo[d]imidazol-2-yl) benzoic acid (2b): White solid, yield 85%; 1H NMR (300 MHz, DMSO-d6). δ 8.27 (d, J = 8.3 Hz, 2H), 8.10 (d, J = 8.4 Hz, 2H), 7.69 (s, 1H), 7.64 (d, J = 8.6 Hz, 1H), 7.26 (dd, J = 8.6, 2.0 Hz, 1H); 13C NMR (101 MHz, DMSO-d6) δ 168.07, 152.25, 133.93, 133.39, 130.36, 129.67, 127.20, 127.04, 123.19; ESI-MS: 273 (M+H)+.
4-(1-phenyl-1H-benzo[d]imidazol-2-yl) benzoic acid (2d): White solid, yield 90%; 1H NMR (500 MHz, DMSO-d6) δ 7.90 (d, J = 8.2 Hz, 2H), 7.83 (d, J = 7.8 Hz, 1H), 7.64 (d, J = 8.3 Hz, 2H), 7.58 (t, J = 8.7 Hz, 3H), 7.47–7.41 (m, 2H), 7.34 (dd, J = 9.7, 8.3 Hz, 2H), 7.23 (d, J = 8.4 Hz, 1H);
13C NMR (100 MHz, DMSO-d6) δ 167.24, 151.33, 142.96, 137.55, 136.61, 134.20, 131.89, 130.60, 129.74, 129.66, 129.48, 127.92, 124.30, 123.49, 120.08, 111.10; ESI-MS: 315 (M+H)+.
General Procedure for the Synthesis of Bbenzimidazoles Amides (3a-3d): Benzoic acid derivative (2a-2d) (0.025 mol) was taken in 100 ml RBF in DMF solvent and EDCI (1.2 Eq) and HOBt was added at r.t to this solution and stirred for 15 minutes. Finally, propargyl amine was added to the mixture and reaction mixture was kept for overnight. Completion of reaction was monitored by TLC. After completion, reaction cool down to room temperature and water and ethyl acetate work up followed by rota-evaporation provide the crude, the crude product was purified by column chromatography to give product (3a-3d). Yield: 83%, white solid.
4-(5-chloro-1H-benzo[d]imidazol-2-yl)-N-(prop-2-yn-1-yl) benzamide (3b): White solid, yield 90%; 1H NMR (300 MHz, DMSO-d6) δ 13.33 (s, 1H), 9.10 (t, J = 5.4 Hz, 1H), 8.26 (d, J = 8.4 Hz, 2H), 8.04 (d, J = 8.4 Hz, 2H), 7.65 (s, 2H), 7.32 – 7.22 (m, 1H), 4.10 (dd, J = 5.3, 2.3 Hz, 2H), 3.15 (t, J = 2.3 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) δ 165.34, 151.70, 134.90, 132.20, 127.97, 126.46, 122.75, 81.15, 72.91, 28.58; ESI-MS: 310 (M+H)+.
4-(1-phenyl-1H-benzo[d]imidazol-2-yl)-N-(prop-2-yn-1-yl) benzamide (3d): White solid, yield 90%; 1H NMR (500 MHz, DMSO) δ 9.00 (t, J = 5.5 Hz, 1H), 7.82 (dd, J = 6.8, 1.8 Hz, 3H), 7.63 – 7.54 (m, 5H), 7.47 – 7.43 (m, 2H), 7.33 (dtd, J = 14.9, 7.2, 1.2 Hz, 2H), 7.23 (d, J = 7.5 Hz, 1H), 4.05 (dd, J = 5.5, 2.5 Hz, 2H), 3.13 (t, J = 2.5 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 165.72, 151.45, 143.02, 137.58, 136.72, 134.84, 132.99, 130.59, 129.55, 129.45, 128.00, 127.73, 124.17, 123.41, 120.04, 111.06, 81.61, 73.42, 40.64, 40.43, 40.22, 40.01, 39.81, 39.60, 39.39, 29.04; ESI-MS: 352 (M+H)+.
General Procedure for the Synthesis of Compounds (4a-4u): Compound (3a-3d) (0.025mol) and different aryl azides (0.025mol) in 5 ml [H2O: tBuOH] solvent was taken with catalytic amount of CuSO4. 5H2O and Sodium ascorbate and stirred for 3-4 hrs. Completion of reaction was checked by TLC. After rotary evaporation, reaction mixture neutralized with NaHCO3 and water (10ml) and chloroform (20ml) were added and the aqueous layer was extracted with chloroform (2 x 25 ml). The combined organic layer was dried over anhydrous Na2SO4 and concentrated by rotary evaporation to afford crude product which was further purified by column chromatography using ethyl acetate and hexane as solvent system.
4-(1H - benzo[d] imidazol-2-yl) - N-((1 - (3, 5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl) methyl) benzamide (4a): White solid (75%); M.P.: 244-246 oC; 1H NMR (300 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.77 (s, 1H), 8.34 (s, 1H), 8.04 (s, 2H), 7.80 (s, 1H), 7.62 (s, 1H), 7.27 (d, J = 24.4 Hz, 2H), 7.06 (d, J = 8.5 Hz, 3H), 6.58 (s, 1H), 4.63 (s, 2H), 3.80 (s, 6H); 13C NMR (75 MHz, DMSO-d6) δ 165.73, 161.12, 138.04, 133.47, 133.13, 129.28, 127.86, 126.14, 123.85, 121.92, 103.84, 100.19, 98.20, 55.63, 34.94; HRMS (ESI) calculated for C25H23O3N6 (M+H)+ 455.1826; found: 455.1818.
4-(1H - benzo[d] imidazol-2-yl) – N - ((1 - (4-methoxyphenyl)-1H-1,2,3-triazol-4-yl) methyl) benzamide (4b): White solid (78%); M.P.: 126-128 oC; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 6.2 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.71 (dd, J = 5.5, 3.4 Hz, 1H), 7.59 (dd, J = 8.7, 4.3 Hz, 3H), 7.53 (dd, J = 5.6, 3.3 Hz, 1H), 7.39 – 7.30 (m, 1H), 7.26 (s, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 4.77 (d, J = 5.3 Hz, 2H), 3.86 (s, 3H);13C NMR (75 MHz, CDCl3+DMSO-d6) δ 161.30, 160.32, 153.38, 143.81, 133.13, 129.16, 127.54, 126.02, 124.59, 122.39, 121.93, 121.61, 119.58, 116.06, 53.85, 38.48; HRMS (ESI) calculated for C24H21O2N6 (M+H)+ 425.1720; found: 425.1717.
4-(1H-benzo[d] imidazol-2-yl) – N - ((1-(4-(trifluoromethyl) phenyl)-1H-1,2,3-triazol-4-yl) methyl) benzamide (4d): White solid (69%); M.P.: 136-138 oC; 1H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 8.88 (s, 1H), 8.24 (t, J = 7.4 Hz, 3H), 8.03 (s, 2H), 7.80 (d, J = 12.3 Hz, 4H), 7.62 (s, 1H), 7.31 (d, J = 7.1 Hz, 1H), 7.07 (d, J = 7.8 Hz, 1H), 4.66 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ 165.67, 165.36, 139.52, 137.07, 135.45, 133.44, 131.22, 130.71, 130.28, 127.88, 126.06, 125.33, 124.98, 123.75, 121.71, 116.45, 111.77, 34.92; HRMS (ESI) calculated for C24H18ON6F3 (M+H)+ 463.1488; found: 463.1484.
N-((1-(3,5-dimethoxyphenyl)-1H-1, 2, 3-triazol-4-yl) methyl)-4-(1-phenyl-1H-benzo[d]imidazol-2-yl) benzamide (4l): White solid (73%); M.P.: 116-118 oC; 1H NMR (300 MHz, DMSO-D6) δ 9.15 (s, 1H), 8.71 (s, 1H), 7.85 (d, J = 7.7 Hz, 3H), 7.57 (d, J = 7.2 Hz, 5H), 7.43 (d, J = 7.0 Hz, 2H), 7.39 – 7.17 (m, 3H), 7.06 (s, 2H), 6.58 (s, 1H), 4.58 (d, J = 4.6 Hz, 2H), 3.81 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 166.96, 161.51, 142.81, 138.39, 136.59, 134.56, 132.94, 130.05, 129.58, 128.87, 127.35, 127.16, 123.87, 123.34, 121.10, 119.97, 110.65, 100.79, 98.96, 55.75, 35.32; HRMS (ESI) calculated for C31H27O3N6 (M+H)+ 531.2139; found: 531.2134.
N-((1-(3,4-dichlorophenyl)-1H-1, 2, 3-triazol-4-yl)methyl)-4-(1-phenyl-1H-benzo[d]imidazol-2-yl) benzamide (4p): White solid (82%); M.P.: 118-120 oC; 1H NMR (400 MHz, CDCl3) δ 8.09 (s, 1H), 7.89 (s, 2H), 7.73 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 1.2 Hz, 2H), 7.52 – 7.47 (m, 3H), 7.36 (t, J = 7.4 Hz, 1H), 7.32 – 7.27 (m, 3H), 7.26 (s, 2H), 4.76 (d, J = 5.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 167.00, 136.62, 135.93, 134.38, 134.06, 133.03, 131.50, 130.07, 129.64, 128.89, 127.36, 127.09, 123.91, 123.38, 122.31, 120.88, 120.00, 119.42, 110.65, 35.33; HRMS (ESI) calculated for C29H21ON6Cl2 (M+H)+ 539.1148; found: 539.1153.
Antimicrobial Activity: Antibacterial properties from the synthesized benzimidazoles based triazole conjugates (4a-4u) was screened by the agar well diffusion method against both Gram-positive bacteria (S. aureus, B. subtilis, M. luteus and B. megatherium) as well as Gram-negative bacteria (E. coli, K. pneumoneae, S. typhi and S. paratyphi). Before analysing the activity, all microorganisms were brought to synchronized growth by inoculating them in nutrient broth and subsequently incubating for 18 hours and used for further activity studies. In brief, nutrient agar medium is prepared, autoclaved and poured in a sterile petri plate under sterile environment.
After solidification, 50 µL (106CFU/mL) of test bacterial culture were inoculated and spread uniformly by sterile spreader and wells were made on agar plate by sterile cork borer. A 100 μg/mL stock solution of test compounds and standard drug streptomycin were prepared using DMSO (Dimethyl sulfoxide) as a solvent. The streptomycin was used as standard as well as positive control whereas neat DMSO was used as negative control. 100 µL of the test samples, streptomycin and DMSO were loaded individually in separate wells. The plates were incubated at 37°C for 18 hours and the zone of inhibition measured by using calibrated scale and expressed in mm.
These results clearly indicate that compounds (4a-4u) displayed significant activity with a high degree of variation. Analysis of antibacterial activity profile of synthesized compounds revealed that compounds (4a) and (4c) exhibited prominent activity against all tested Gram positive and Gram-negative microbes Table 1 suggesting similar growth inhibitory potential like that of streptomycin.
TABLE 1: ANTIBACTERIAL ACTIVITIES OF COMPOUNDS BY THE AGAR WELL DIFFUSION METHOD DATA REPRESENTED AS ZONE OF INHIBITION (MM)
Compound | S. aureus | B. subtilis | M. luteus | B. megatherium | E. coli | K. pneumonia | S. typhi | S. Para typhi |
4a | 22 | 19 | 20 | 20 | 18 | 22 | 12 | 14 |
4b | 14 | 13 | 14 | 17 | 15 | 15 | 13 | 16 |
4c | 20 | 11 | 16 | 16 | 15 | 16 | 0 | 15 |
4d | 14 | 15 | 15 | 11 | 14 | 12 | 16 | 13 |
4e | 16 | 16 | 13 | 0 | 0 | 12 | 11 | 10 |
4f | 15 | 12 | 10 | 9 | 16 | 13 | 15 | 0 |
4g | 13 | 12 | 0 | 11 | 11 | 0 | 16 | 7 |
4h | 10 | 13 | 7 | 15 | 0 | 11 | 12 | 14 |
4i | 0 | 0 | 8 | 16 | 11 | 0 | 12 | 16 |
4j | 7 | 0 | 11 | 12 | 18 | 13 | 13 | 15 |
4k | 11 | -- | -- | - | -- | -- | - | -- |
4l | 15 | 0 | 14 | 0 | 14 | 17 | 10 | 14 |
4m | 11 | 11 | 15 | 11 | 9 | 0 | 17 | 16 |
4n | 10 | 16 | 15 | 16 | 13 | 8 | 11 | 15 |
4o | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
4p | 16 | 11 | 11 | 12 | 14 | 13 | 11 | 11 |
4q | 11 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
4r | 0 | -- | -- | -- | -- | -- | -- | -- |
4s | 9 | 8 | 9 | 8 | 11 | 11 | 9 | 10 |
4t | 0 | 8 | 8 | 0 | 9 | 0 | 0 | 8 |
4u | 10 | 9 | 8 | 0 | 0 | 8 | 9 | 10 |
Streptomycin | 23 | 24 | 26 | 21 | 24 | 23 | 20 | 22 |
“ --“ : not tested.
In view of the above results, further evaluation is under progress to understand the required concentration essential for complete inhibition of growth of selected microbial strain i.e., MIC.
CONCLUSION: Benzimidazoles linked triazole hybrids (4a-4u) have been synthesized by simple cyclization, followed by amide coupling and click reaction starting from o-phenylene diamines as substrates. Further, these compounds were evaluated for their anti-microbial activity by using the agar well diffusion method. Most of the compounds were found to be significant in view of inhibition in the range between 8-25mm against both Gram-positive and Gram-negative bacterial strains. Based on this primary result, further studies are under progress.
ACKNOWLEDGEMENT: Author Abdul Rahim Abdul Sami is thankful to the Principals, Maulana Azad College of Arts, Science & Commerce, Aurangabad and Milliya Arts, Science & Management Science College, Beed for providing necessary facilities for this research work.
CONFLICT OF INTEREST: The authors declare no conflict of interest.
REFERENCES:
- Alkhzem AH, Woodman TJ and Blagbrough IS: “Design and synthesis of hybrid compounds as novel drugs and medicines,” RSC Adv 2022; 12(30): 19470–19484, doi: 10.1039/d2ra03281c.
- Panigrahi D, Mishra A and Sahu SK: “Pharmacophore modelling, QSAR study, molecular docking and in-silico ADME prediction of 1,2,3-triazole and pyrazolopyridones as DprE1 inhibitor antitubercular agents,” SN Appl Sci 2020; 2(5): 1–28, doi: 10.1007/s42452-020-2638-y.
- Tahlan S, Kumar S and Narasimhan B: “Pharmacological significance of heterocyclic 1H-benzimidazole scaffolds: a review.” BMC Chem 2019; 13(1): 1–21, doi: 10.1186/s13065-019-0625-4.
- Wright JB: “The chemistry of the benzimidazoles,” Chem. Rev 1951; 48(3): 397–541, doi: 10.1021/cr60151a002.
- Vistoli G, Pedretti A and Testa B: “Assessing drug-likeness – what are we missing?,” Drug Discov. Today 2008; 13(7–8): 285–294. doi: 10.1016/J.DRUDIS.2007.11.007.
- Bozorov K, Zhao J and Aisa HA: “1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview.” Bioorganic Med Chem 2019; 27(16): 3511–3531, doi: 10.1016/j.bmc.2019.07.005.
- Santos CS, De Oliveira RJ, De Oliveira RN and Freitas JCR: “1,2,3- Triazoles: General and key synthetic strategies,” Arkivoc 2020; 2020: 219–271, doi: 10.24820/ARK.5550190.P011.293.
- Singh G: “CuAAC ensembled 1,2,3-triazole linked nanogels for targeted drug delivery: a review.” RSC Adv 2023; 13(5): 2912–2936, doi: 10.1039/d2ra05592a.
- Recnik L, Kandioller W and Mindt TL: “Surrogates for the stabilisation of linear peptides.” Molecules 2020; 25: 1–26.
- Pokhodylo N: “Novel N-(4-thiocyanatophenyl)-1H-1,2,3-triazole-4-carboxamides exhibit selective cytotoxic activity at nanomolar doses towards human leukemic T-cells.” Eur J Med Chem 2022; 241. doi: 10.1016/j.ejmech.2022.114633.
- Alam MM: “1,2,3-Triazole hybrids as anticancer agents: A review,” Arch. Pharm. (Weinheim) 2022; 355: 1, doi: 10.1002/ardp.202100158.
- Hryhoriv H: “The Search for New Antibacterial Agents among 1,2,3-Triazole functionalized ciprofloxacin and norfloxacin hybrids: synthesis, docking studies, and biological activity evaluation.” 2022; Sci Pharm 90(1): doi: 10.3390/scipharm90010002.
- Sadek and Kamal Usef: "Recent developments in the synthesis of hybrid heterocycles, a promising approach to develop multi-target antibacterial agents." Journal of Molecular Structure 2023; 1286: 135616.
- Marinescu M: "Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review. Antibiotics 2023; 12: 1220.
- Hoffmann, Torsten and Rainer Metternich: "The future of medicinal chemistry." Angewandte Chemie International Edition 2012; 51(35): 8670-8671.
- Shankar and Ravi: "Synthesis and biological evaluation of 3, 4, 6-triaryl-2-pyranones as a potential new class of anti-breast cancer agents." Bioorganic & Medicinal Chemistry 2009; 17(11): 3847-3856.
- Vila JORDI: Javier moreno-morales, and clara ballesté-delpierre. "current landscape in the discovery of novel antibacterial agents." Clinical Microbiology and Infection 2020; 26 (5): 596-603.
- Berlin, Cameron B, Eesha Sharma and Marisa C: Kozlowski. "Quantification of hydrogen-bond-donating ability of biologically relevant compounds." The Journal of Organic Chemistry 2024; 89(7): 4684-4690.
- Stockwell and Brent R: "Privileged scaffolds for library design and drug discovery Matthew E Welsch, Scott A Snyder and Brent R Stockwell." Current Opinion in Chemical Biology 2010; 141-15.
- Kumar and Aman: "A mini review on pharmacological significance of isatin-1, 2, 3-triazole hybrids." Current Topics in Medicinal Chemistry 2023; 23(10): 833-847.
- Zala and Ajayrajsinh R: "Design and synthesis of novel 1, 2, 3-triazole linked hybrids: Molecular docking, MD simulation, and their antidiabetic efficacy as α-Amylase inhibitors." J of Molecular Structure 2023; 1285: 135493.
- Goyal, Akshi and Meena Bhandari: "Synthetic and therapeutic review of triazoles and hybrids." Heterocyclic Communications 2024; 30(1): 20220174.
- Bohacek, Regine S and Colin McMartin: "Modern computational chemistry and drug discovery: structure generating programs." Current Opinion in Chemical Biology 1997; 1(2): 157-161.
- Dalvie and Deepak K: "Biotransformation reactions of five-membered aromatic heterocyclic rings." Chemical research in toxicology 2002; 15(3): 269-299.
- Alzhrani, Zohor MM, Mohammad M. Alam and Syed Nazreen: "Recent advancements on benzimidazole: A versatile scaffold in medicinal chemistry." Mini Reviews in Medicinal Chemistry 2022; 22(2): 365-386.
- Fonkui and Thierry Youmbi: "Benzimidazole Schiff base derivatives: synthesis, characterization and antimicrobial activity." BMC Chemistry 2019; 13: 1-11.
How to cite this article:
Khan AJ and Sami ARA: An efficient synthesis, characterization and bioactivity of benzimida-zole linked triazoles. Int J Pharm Sci & Res 2025; 16(1): 234-40. doi: 10.13040/IJPSR.0975-8232.16(1).234-40.
All © 2025 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
28
234-240
636 KB
24
English
IJPSR
Asghar Jafar Khan and Abdul Rahim Abdul Sami *
Department of Chemistry, Milliya Arts, Scince & Mangement Science College, Beed, Maharashtra, India.
phychemmax@gmail.com
01 August 2024
04 September 2024
24 September 2024
10.13040/IJPSR.0975-8232.16(1).234-40
01 January 2025