How to cite this paper
Atif, A., Ahmed, B., Sir, H., Mohammed, S & Abdellah, Z. (2026). Synthesis, characterization and computational investigation of 5-chloro-2-(5-(2-methyl-1H-benzimidazol-5-yl)-1,3,4-oxadiazol-2-yl)aniline: DFT, parr indices, ADMET, molecular docking and molecular dynamics.Current Chemistry Letters, 15(1), 101-116.
Refrences
1. Atif A., El Alami A., and Ait Sir H. (2025) Minireview of Synthesis Process of 1.3.4-Thiadiazole Derivatives. Chem. Afr., 8 (7) 1-24.
2. Atif A., and Ait Sir H. (2025) Progress in the Synthesis of Tetrazoles, A Brief Review. Org. Prep. Proced. Int.
3. Atif A., and Ait Sir H. (2025) Synthetic Approaches for Oxazole Derivatives: A Review. Journal of Heterocyclic Chemistry, 1–26
4. Atif A., Ameur S., and Ait Sir H. (2025) Synthesis. characterization and in silico evaluation of 2.5-bis(2-(trifluoromethyl)-1Hbenzimidazol-5-yl)-1.3.4-oxadiazole: Reactivity. ADME/toxicity. and docking against therapeutic targets. Curr. Chem. Lett., 14 (4) 793-804
5. Atif A., El Alami A., Youssoufi F., Jebbari S., and Ait Sir H. (2025). Review of synthesis process of 1.3.4-oxadiazole analogs. Curr. Chem. Lett., 14 (2) 339–364
6. Atif A., Ameur S., and Ait Sir H. (2025) Synthesis. Characterization. and Computational Investigation of 2.5-Bis(2-Methyl-1H-benzimidazol-5-yl)-1.3.4-oxadiazole: Quantum Chemical Analysis. ADME Prediction. Molecular Docking. and MD-Based Corrosion Study for Photonic and Therapeutic Applications. Curr. Chem. Lett.
7. Tokmajyan G. G., and Karapetyan L. V. (2025) Methods of synthesis of furan-2 (5 H)-ones. Chem. Heterocycl. Compd., 61 (2025) 73-100.
8. Mitra A. K., and Ghosh A. (2025) Perspective on Biginelli reaction: en route toward the development of biologically and industrially relevant dihydropyrimidone-based frameworks. Chem. Heterocycl. Compd., 61 (2025) 155-187
9. Tokmajyan G. G., and Karapetyan L. V. (2025) Chemical transformations of furan-2 (5 H)-ones. Chem. Heterocycl. Compd., 61 (2025) 101-129.
10. Jasiński R. (2025) Recent progress in the synthesis of nitropyrrolidines via noncatalyzed (3+ 2) cycloaddition reactions of azomethine ylides (microreview). Chem. Heterocycl. Compd., 61 (2025) 240-242.
11. Łapczuk A. (2023) The [3+ 2] cycloaddition reaction as an attractive way for the preparation of nicotine analogs (microreview). Chem. Heterocycl. Compd., 59 (3) 109-111.
12. Sadowski M., and Kula K. (2024) Unexpected course of reaction between (1E. 3E)-1. 4-Dinitro-1. 3-butadiene and n-methyl azomethine ylide—a comprehensive experimental and quantum-chemical study. Molecules, 29 (21) 5066-5090.
13. Aggarwal N., Kumar R., Dureja P., and Khurana J. M. (2012) Synthesis of novel nalidixic acid-based 1.3.4-thiadiazole and 1.3.4-oxadiazole derivatives as potent antibacterial agents. Chem. Biol. Drug Des., 79 (4) 384-397.
14. Chawla G., Kumar U., Bawa S., and Kumar J. (2012) Syntheses and evaluation of anti-inflammatory. analgesic and ulcerogenic activities of 1. 3. 4-oxadiazole and 1. 2. 4-triazolo [3. 4-b]-1.3.4-thiadiazole derivatives. J. Enzyme Inhib. Med. Chem., 27 (5) 658-665.
15. Chen C. J., Song B. A., Yang S., Xu G. F., Bhadury P. S., Jin L. H., Hu D. Y., Li Q. Z., Liu F., Xue W., Lu P., and Chen Z. (2007) Synthesis and antifungal activities of 5-(3. 4. 5-trimethoxyphenyl)-2-sulfonyl-1.3.4-thiadiazole and 5-(3.4.5-trimethoxyphenyl)-2-sulfonyl-1. 3. 4-oxadiazole derivatives. Bioorg. Med. Chem., 15 (12) 3981-3989.
16. El-Essawy F. A., El-Sayed W. A., El-Kafrawy S. A., Morshedy A. S., and Abdel-Rahman A. H. (2008) Anti-hepatitis B virus activity of new 1. 2. 4-triazol-2-yl-and 1. 3. 4-oxadiazol-2-yl-2-pyridinone derivatives. Z. Naturforsch. C., 63 (9-10) 667-674.
17. Fan Z., Shi Z., Zhang H., Liu X., Bao L., Ma L., Zuo X., Zheng Q., and Mi N. (2009) Synthesis and biological activity evaluation of 1.2.3-thiadiazole derivatives as potential elicitors with highly systemic acquired resistance. J. Agric. Food Chem., 57 (10) 4279-4286.
18. Garzón A., Granadino-Roldán J. M., Moral M., García G., Fernández-Liencres M. P., Navarro A., Ruiz T. P., and Fernández-Gómez M. (2010) Density functional theory study of the optical and electronic properties of oligomers based on phenyl-ethynyl units linked to triazole. thiadiazole. and oxadiazole rings to be used in molecular electronics. J. Chem. Phys., 132(6) 064901-064913.
19. Gilani S. J., Khan S. A., Alam O., and Siddiqui N. (2011) Synthesis and in vitro antimicrobial evaluation of condensed heterocyclic 6-substituted 1. 2. 4-triazolo-[3. 4-b]-1. 3. 4-thiadiazole and 1.3.4-oxadiazole derivatives of isoniazid. Acta Pol Pharm., 68 (2) 205-211.
20. Küçükgüzel Ş. G., Küçükgüzel I., Tatar E., Rollas S., Şahin F., Güllüce M., Clercq E. D., and Kabasakal L. (2007) Synthesis of some novel heterocyclic compounds derived from diflunisal hydrazide as potential anti-infective and anti-inflammatory agents. Eur. J. Med. Chem., 42 (7) 893-901.
21. Li Y., Geng J., Liu Y., Yu S., and Zhao G. (2013) Thiadiazole—A promising structure in medicinal chemistry. ChemMedChem., 8 (1) 27-41.
22. Mullican M. D., Wilson M. W., Conner D. T., Kostlan C. R., Schrier D. J., and Dyer R. D. (1993) Design of 5-(3. 5-di-tert-butyl-4-hydroxyphenyl)-1. 3. 4-thiadiazoles.-1. 3. 4-oxadiazoles. and-1. 2. 4-triazoles as orally active. nonulcerogenic antiinflammatory agents. J. Med. Chem., 36 (8) 1090-1099.
23. Mylari B. L., Beyer T. A., Scott P. J., Aldinger C. E., Dee M. F., Siegel T. W., and Zembrowski W. J. (1992) Potent. orally active aldose reductase inhibitors related to zopolrestat: surrogates for benzothiazole side chain. J. Med. Chem., 35 (3) 457-465.
24. Padmaja A., Muralikrishna A., Rajasekhar C., and Padmavathi V. (2011) Synthesis and antimicrobial activity of pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1. 3. 4-oxadiazoles. 1. 3. 4-thiadiazoles and 1. 2. 4-triazoles. Chem. Pharm. Bull., 59 (12) 1509-1517.
25. Rajak H., Agarawal A., Parmar P., Thakur B. S., Veerasamy R., Sharma P. C., and Kharya M. D. (2011) 2. 5-Disubstituted-1. 3. 4-oxadiazoles/thiadiazole as surface recognition moiety: Design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors. Bioorg. Med. Chem. Lett., 21 (19) 5735-5738.
26. Holla B. S., Gonsalves R., and Shenoy S. (2000) Synthesis and antibacterial studies of a new series of 1. 2-bis (1. 3. 4-oxadiazol-2-yl) ethanes and 1. 2-bis (4-amino-1. 2. 4-triazol-3-yl) ethanes. Eur. J. Med. Chem., 35 (2) 267-271.
27. Şahin G., Palaska E., Ekizoğlu M., and Özalp M. (2002) Synthesis and antimicrobial activity of some 1. 3. 4-oxadiazole derivatives. Il Farmaco. 57 (7) 539-542.
28. Macaev F., Rusu G., Pogrebnoi S., Gudima A., Stingaci E., Vlad L., Shvets N., Kandemirli F., Dimoglo A., and Reynolds R. (2005) Synthesis of novel 5-aryl-2-thio-1. 3. 4-oxadiazoles and the study of their structure–anti-mycobacterial activities. Bioorg. Med. Chem., 13 (16) 4842-4850.
29. Tale R. H., Rodge A. H., Keche A. P., Hatnapure G. D., Padole P. R., Gaikwad G. S., and Turkar. S. S. (2011) Synthesis and anti-bacterial. anti-fungal activity of novel 1. 2. 4-oxadiazole. J. Chem. Pharm. Res., 3 (2) 496-505.
30. Zou X. J., Lai L. H., Jin G. Y., and Zhang Z. X. (2002) Synthesis. fungicidal activity. and 3D-QSAR of pyridazinone-substituted 1. 3. 4-oxadiazoles and 1. 3. 4-thiadiazoles. J. Agric. Food Chem., 50 (13) 3757-3760.
31. Burbuliene M. M., Jakubkiene V., Mekuskiene G., Udrenaite E., Smicius R., and Vainilavicius P. (2004) Synthesis and anti-inflammatory activity of derivatives of 5-[(2-disubstitutedamino-6-methyl-pyrimidin-4-yl)-sulfanylmethyl]-3H-1. 3. 4-oxadiazole-2-thiones. Il Farmaco. 59 (10) 767-774.
32. Palaska E., Şahin G., Kelicen P., Durlu N. T., and Altinok G. (2002) Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides. 1. 3. 4-oxadiazoles. 1. 3. 4-thiadiazoles and 1. 2. 4-triazole-3-thiones. Il Farmaco. 57 (2) 101-107.
33. Amir M., and Shikha K. (2004) Synthesis and anti-inflammatory. analgesic. ulcerogenic and lipid peroxidation activities of some new 2-[(2. 6-dichloroanilino) phenyl] acetic acid derivatives. Eur. J. Med. Chem., 39 (6) 535-545.
34. Zarghi A., Tabatabai S. A., Faizi M., Ahadian A., Navabi P., Zanganeh V., and Shafiee A. (2005) Synthesis and anticonvulsant activity of new 2-substituted-5-(2-benzyloxyphenyl)-1. 3. 4-oxadiazoles. Bioorg. Med. Chem. Lett.. 15 (7) 1863-1865.
35. Almasirad A., Tabatabai S. A., Faizi M., Kebriaeezadeh A., Mehrabi N., Dalvandi A., and Shafiee. A. (2004) Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy) phenyl]-1. 3. 4-oxadiazoles and 1. 2. 4-triazoles. Bioorg. Med. Chem. Lett.. 14 (24) 6057-6059.
36. Ainsworth C., and Hackler R. E. (1966) Alkyl-1. 3. 4-oxadiazoles. J. Org. Chem., 31 (10) 3442-3444.
37. Vaidya A., Pathak D., and Shah K. (2021) 1. 3. 4-oxadiazole and its derivatives: A review on recent progress in anticancer activities. Chem. Biol. Drug Des.. 97 (3) 572-591.
38. Siwach A., and Verma P. K. (2020) Therapeutic potential of oxadiazole or furadiazole containing compounds. BMC chemistry. 14 (1) 70-110.
39. VandeVondele J., Krack M., Mohamed F., Parrinello M., Chassaing T., and Hutter J. (2005) Quickstep: Fast and accurate density functional calculations using a mixed Gaussian and plane waves approach. Comput. Phys. Commun., 167 (2) 103-128.
40. Becke A. D. (1993) Density‐functional thermochemistry. III. The role of exact exchange. J. Chem. Phys., 98 (7) 5648-5652.
41. Ulufer-bulut S., Kotan G., and Yuksek H. (2021) Theoretical (6-311G (d. p)/3-21G) and Spectroscopic (13C/1H-NMR. FT-IR) Analyses pf 3-Propyl-4-[3-(2-Methylbenzoxy)-Benzylidenamino]-4. 5-Dihydro-1h-1. 2. 4-Triazol-5-One Molecule. eurasia proc. sci. technol. eng. math.. 15 (2021) 42-53.
42. Aytemız F., Beytur M., and Yuksek H. (2022) Experimentical and Gaussian calculations of 3-Ethyl-4-(2-benzenesulfonyloxy)-benzylideneamino-4. 5-dihydro-1H-1. 2. 4-triazol-5-one. eurasia proc. sci. technol. Eng. Math., 20 (2022) 103-111.
43. Krishnan R. B. J. S., Binkley J. S., Seeger R., and Pople J. A. (1980) Self‐consistent molecular orbital methods. XX. A basis set for correlated wave functions. J. Chem. Phys., 72 (1) 650-654.
44. Kazachenko A. S., Akman F., Abdelmoulahi H., Issaoui N., Malyar Y. N., Al-Dossary O., and Wojcik M. J. (2021) Intermolecular hydrogen bonds interactions in water clusters of ammonium sulfamate: FTIR. X-ray diffraction. AIM. DFT. RDG. ELF. NBO analysis. J. Mol. Liq., 342 (2021) 117475-117499.
45. Mazumdar P., Kashyap A., and Choudhury D. (2023) Investigation of hydrogen bonding in small nucleobases using DFT. AIM. NCI and NBO technique. Comput. Theor. Chem., 1226 (2023) 114188-114197.
46. Ojuka P., Kimani N. M., Apollo S., Nyariki J., Ramos R. S., and Santos C. B. (2023) Phytochemistry of plants in the genus Vepris: A review and in silico analysis of their ADMET properties. S. Afr. J. Bot., 157 (2023) 106-114.
47. Kaul S., Kumar A., Sain B., and Bhatnagar A. K. (2007) Simple and convenient one-pot synthesis of benzimidazoles and benzoxazoles using N. N-Dimethylchlorosulfitemethaniminium chloride as condensing agent. Synth. Commun., 37 (15) 2457-2460.
48. Phillips M. A. (1928) CCCXVII.—The formation of 2-substituted benziminazoles. J. Chem. Soc., 2393-2399.
49. Galal S. A., Hegab K. H., Kassab A. S., Rodriguez M. L., Kerwin S. M., El-Khamry A. M. M. A., and El Diwani H. I. (2009) New transition metal ion complexes with benzimidazole-5-carboxylic acid hydrazides with antitumor activity. Eur. J. Med. Chem., 44(4) 1500-1508.
50. Atif A., Ameur S., Bendaoud A., Hsissou R., Jebbari S., Ait Sir H., and Salah M. (2025) Comprehensive evaluation of a benzimidazole-1.3.4-oxadiazole derivative for corrosion protection of C38 steel in HCl: Experimental. molecular dynamics. monte carlo. and in silico pharmacokinetic approaches. Curr. Chem. Lett., 14 (4) 777-792
51. Atif A., Zahm S., Jebbari S., El Alami A., Youssoufi F., Ait Sir H., Kerraj S., and Salah. M. (2023) synthesis. admet. docking and molecular dynamics of new molecules derivatives from 1.3.4-oxadiazole and 1.3.4-bisoxadiazole: new compounds against hiv. Eur. Chem. Bull., 12 (12) 4139 – 4156
52. Atif A., Marghich M., Nabil N., El Alami A., Daoudi N., Harit T., Youssoufi F., Salah M., Bitar A., and Ait Sir H. (2025) Design. synthesis. and antidiabetic evaluation of novel 1.3-di(1.3.4-oxadiazol-2-yl)benzene derivatives as potent pancreatic α-amylase inhibitors: In vitro and in silico approaches. Curr. Chem. Lett.
53. Elhorri A. M., Belaid K. D., Zouaoui–Rabah M., and Chadli R. (2018) Theoretical study of the azo dyes dissociation by advanced oxidation using Fukui indices. DFT calculations. Comput. Theor. Chem., 1130 (2018) 98-106.
54. Isravel A. D., Jeyaraj J. K., Thangasamy S., and John W. J. (2021) DFT. NBO. HOMO-LUMO. NCI. stability. Fukui function and hole–Electron analyses of tolcapone. Comput. Theor. Chem., 1202 (2021) 113296-113307.
55. Cao Y., Malekshah R. E., Heidari Z., Pelalak R., Marjani A., and Shirazian S. (2021) Molecular dynamic simulations and quantum chemical calculations of adsorption process using amino-functionalized silica. J. Mol. Liq.. 330 (2021) 115544-115557.
56. Khaled K. F., and El-Maghraby A. (2014) Experimental. Monte Carlo and molecular dynamics simulations to investigate corrosion inhibition of mild steel in hydrochloric acid solutions. Arab. J. Chem.. 7 (3) 319-326.
57. Domingo L. R., Pérez P., and Sáez J. A. (2013) Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Adv., 3 (5) 1486-1494.
58. Figueroa-Valverde L., Díaz-Cedillo F., Camacho-Luis A., López Ramos M., and Garcia Cervera E. (2010) Synthesis of a dihydrotestosterone–ciprofloxacin conjugate: relationship between descriptors log P. π. R m. and V m and its antibacterial activity in S. aureus and E. coli. Monatsh. Chem., 141 (3) 373-380.
59. Abdolhosseini M., Zamani H., and Salehzadeh A. (2019) Synergistic antimicrobial potential of ciprofloxacin with silver nanoparticles conjugated to thiosemicarbazide against ciprofloxacin resistant Pseudomonas aeruginosa by attenuation of MexA-B efflux pump genes. Biologia. 74 (9) 1191-1196.
60. Thai, T., Salisbury, B. H., & Zito, P. M. (2025). Ciprofloxacin. In StatPearls. StatPearls Publishing. Retrieved October 24, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK482441/
61. « RCSB PDB: Homepage ». Consulté le: 22 octobre 2025. [En ligne]. Disponible sur: https://www.rcsb.org/
62. Sharma S., Sharma A., and Gupta U. (2021) Molecular Docking studies on the Anti-fungal activity of Allium sativum (Garlic) against Mucormycosis (black fungus) by BIOVIA discovery studio visualizer 21.1. 0.0.
63. Gilad Y., Tuchinsky H., Ben-David G., Minnes R., Gancz A., Senderowitz H., Luboshits G., Firer M. A., and Gellerman. G. (2017) Discovery of potent molecular chimera (CM358) to treat human metastatic melanoma. Eur. J. Med. Chem., 138 (2017) 602-615.
64. Wang Q., He J., Wu D., Wang J., Yan J., and Li H. (2015) Interaction of α-cyperone with human serum albumin: Determination of the binding site by using Discovery Studio and via spectroscopic methods. J. Lumin., 164 (2015) 81-85.
65. Mouhib A., Kadiri F., Yamari I., Es-Sounni B., Raji H., El Abbouchi A., El Kazzouli S., Chegdani F., El Yazidi M., Mazoir N., Chtita S., and Bakhouch M. (2025) Novel Hybrids-based quinazolinone: Synthesis. characterization. in vitro and in silico antibacterial investigations. J. Indian Chem. Soc., 102 (9) 101934-101952.
66. Chen X., Chen Y., Cui J., Li Y., Liang Y., and Cao G. (2021) Molecular dynamics simulation and DFT calculation of “green” scale and corrosion inhibitor. Comput. Mater. Sci., 188, 110229.
67. Ahmad Z. U., Chao B., Konggidinata M. I., Lian Q., Zappi M. E., and Gang D. D. (2018) Molecular simulation and experimental validation of resorcinol adsorption on Ordered Mesoporous Carbon (OMC). J. Hazard. Mater., 354 (2018) 258-265.
68. Belghiti M. E., Bouazama S., Echihi S., Mahsoune A., Elmelouky A., Dafali A., Emran K. M., Hammouti B., and Tabyaoui M. (2020) Understanding the adsorption of newly Benzylidene-aniline derivatives as a corrosion inhibitor for carbon steel in hydrochloric acid solution: Experimental. DFT and molecular dynamic simulation studies. Arab. J. Chem., 13 (1) 1499-1519.
69. Shokry H. (2014) Molecular dynamics simulation and quantum chemical calculations for the adsorption of some Azo-azomethine derivatives on mild steel. J. Mol. Struct., 1060 (2014) 80-87.
70. El-Hajjaji F., Messali M., Aljuhani A., Aouad M. R., Hammouti B., Belghiti M. E., Chauhan D. S., and Quraishi M. A. (2018) Pyridazinium-based ionic liquids as novel and green corrosion inhibitors of carbon steel in acid medium: electrochemical and molecular dynamics simulation studies. J. Mol. Liq., 249 (2018) 997-1008.
71. Beniken M., Salim R., Ech–chihbi E., Sfaira M., Hammouti B., Touhami M. E., Mohsin M. A., and Taleb M. (2022) Adsorption behavior and corrosion inhibition mechanism of a polyacrylamide on C–steel in 0.5 M H2SO4: Electrochemical assessments and molecular dynamic simulation. J. Mol. Liq., 348 (2022) 118022-118036.