Computational Studies and Antimicrobial Activity of 1-(benzo[d]oxazol-2- yl)-3,5-diphenylformazan Derivatives


Cite item

Full Text

Abstract

Background:Due to the biological importance of the benzoxazole derivatives, some 1- (benzo[d]oxazol-2-yl)-3,5-diphenyl-formazans 4a-f were synthesized and screened for in-silico studies and in-vitro antibacterial activity.

Methods:The benzo[d]oxazole-2-thiol (1) was prepared by reacting with 2-aminophenol and carbon disulfide in the presence of alcoholic potassium hydroxide. Then 2-hydrazinylbenzo[d] oxazole (2) was synthesized from the reaction of compound 1 with hydrazine hydrate in the presence of alcohol. Compound 2 was reacted with aromatic aldehydes to give Schiff base, 2-(2- benzylidene-hydrazinyl)benzo[d]oxazole derivatives 3a-f. The title compounds, formazan derivatives 4a-f, were prepared by a reaction of benzene diazonium chloride. All compounds were confirmed by their physical data, FTIR, 1H-NMR, and 13CNMR spectral data. All the prepared title compounds were screened for in-silico studies and in-vitro antibacterial activity on various microbial strains.

Results:Molecular docking against the 4URO receptor demonstrated that molecule 4c showed a maximum dock score of (-) 8.0 kcal/mol. MD simulation data reflected the stable ligand-receptor interaction. As per MM/PBSA analysis, the maximum free binding energy of (-) 58.831 kJ/mol was exhibited by 4c. DFT calculation data confirmed that most of the molecules were soft molecules with electrophilic nature.

Conclusion:The synthesized molecules were validated using molecular docking, MD simulation, MMPBSA analysis, and DFT calculation. Among all the molecules, 4c showed maximum activity. The activity profile of the synthesized molecules against tested micro-organisms was found to be 4c>4b>4a>4e>4f>4d.

About the authors

Mazen Almehmadi

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University

Email: info@benthamscience.net

Ahad Alsaiari

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University

Email: info@benthamscience.net

Mamdouh Allahyani

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University

Email: info@benthamscience.net

Abdulaziz Alsharif

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences,, Taif University

Email: info@benthamscience.net

Abdulelah Aljuaid

Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University

Email: info@benthamscience.net

Supriyo Saha

Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University

Email: info@benthamscience.net

Mohammad Asif

Era College of Pharmacy, Era University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Kakkar, S.; Tahlan, S.; Lim, S.M.; Ramasamy, K.; Mani, V.; Shah, S.A.A.; Narasimhan, B. Benzoxazole derivatives: design, synthesis and biological evaluation. Chem. Cent. J., 2018, 12(1), 92. doi: 10.1186/s13065-018-0459-5 PMID: 30101384
  2. Li, Z.; Dong, J.; Yuan, Z.; Yang, D.Y.; Weng, Z. One-pot synthesis of 3-difluoromethyl benzoxazole-2-thiones. Org. Lett., 2018, 20(20), 6407-6410. doi: 10.1021/acs.orglett.8b02713 PMID: 30303015
  3. Evans, D.A.; Sacks, C.E.; Kleschick, W.A.; Taber, T.R. Polyether antibiotics synthesis. Total synthesis and absolute configuration of the ionophore A-23187. J. Am. Chem. Soc., 1979, 101(22), 6789-6791. doi: 10.1021/ja00516a069
  4. Sharma, N.K.P.; Jha, K.K.; Kumar, M.V. Synthesis and antimicrobial evaluation of 2-(2-(benzo d oxazol-2-yl) phenylamino)-n-(substituted phenyl) acetamides. Int. J. Pharm. Sci. Res., 2014, 5(8), 3260-3266.
  5. Lavanya, A.; Parlapalli, A.; Ciddi, M.; Sarangapani, M. Novel 2–amino-n’-(2-oxoindolin–3-ylidene) benzodoxazol-5-carbohydrazides as anti-inflammatory agents. Int. J. Pharm. Sci. Res., 2015, 6(1), 212-218.
  6. Davidson, J.P.; Corey, E.J. First enantiospecific total synthesis of the antitubercular marine natural product pseudopteroxazole. Revision of assigned stereochemistry. J. Am. Chem. Soc., 2003, 125(44), 13486-13489. doi: 10.1021/ja0378916 PMID: 14583045
  7. Kakkar, S.; Kumar, S.; Narasimhan, B.; Lim, S.M.; Ramasamy, K.; Mani, V.; Shah, S.A.A. Design, synthesis and biological potential of heterocyclic benzoxazole scaffolds as promising antimicrobial and anticancer agents. Chem. Cent. J., 2018, 12(1), 96-107. doi: 10.1186/s13065-018-0464-8 PMID: 30232633
  8. Xiao, Y.; Jing, B.; Liu, X.; Xue, H.; Liu, Y. Metal-free C–H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source. Beilstein J. Org. Chem., 2019, 15, 279-284. doi: 10.3762/bjoc.15.24 PMID: 30800177
  9. Abeed, A.; Youssef, M.; Hegazy, R. Synthesis, Anti-diabetic and renoprotective activity of some new benzazole, thiazolidin-4-one and azetidin-2-one derivatives. J. Braz. Chem. Soc., 2017, 28(11), 2054-2063. doi: 10.21577/0103-5053.20170050
  10. Akbay, A.; Oren, I.; Temiz-Arpaci, O.; Aki-Sener, E.; Yalçin, I. Synthesis and HIV-1 reverse transcriptase inhibitor activity of some 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole and oxazolo(4,5-b)pyridine derivatives. Arzneimittelforschung, 2003, 53(4), 266-271. PMID: 12785123
  11. Sangi, D.P.; Meira, Y.G.; Moreira, N.M.; Lopes, T.A.; Leite, M.P.; Pereira-Flores, M.E.; Alvarenga, E.S. Benzoxazoles as novel herbicidal agents. Pest Manag. Sci., 2019, 75(1), 262-269. doi: 10.1002/ps.5111 PMID: 29885098
  12. Sato, H.; Dan, T.; Onuma, E.; Tanaka, H.; Aoki, B.; Koga, H. Studies on Uricosuric Diuretics. II. Substituted 7,8-Dihydrofuro(2,3-g)-1,2-benzisoxazole-7-carboxylic acids and 7,8-Dihydrofuro(2,3-g)benzoxazole-7-carboxylic acids. Chem. Pharm. Bull. (Tokyo), 1991, 39(7), 1760-1772. doi: 10.1248/cpb.39.1760 PMID: 1777929
  13. Kumar, T.K.; Sreenivasulu, R. Synthesis, characterization and antimicrobial activity of novel n-(benzoxazol-2-yl)-2-(2-oxoindolin-3-ylidine) hydrazine carbothioamides. Int. J. Pharm. Sci. Res., 2020, 11(6), 2776-2785.
  14. Turan-Zitouni, G.; Demirayak, Ş.; Özdemir, A.; Kaplancıklı, Z.A.; Yıldız, M.T. Synthesis of some 2-(benzazole-2-yl)thioacetylaminothiazole derivatives and their antimicrobial activity and toxicity. Eur. J. Med. Chem., 2004, 39(3), 267-272. doi: 10.1016/j.ejmech.2003.11.001 PMID: 15051175
  15. Suto, M.J.; Turner, W.R. Synthesis of Boxazomycin B and related analogs. Tetrahedron Lett., 1995, 36(40), 7213-7216. doi: 10.1016/0040-4039(95)01533-N
  16. Lewis, J.W.; Sandorfy, C. Infrared absorption and resonance Raman scattering of photochromic triphenylformazans. Can. J. Chem., 1983, 61(5), 809-816. doi: 10.1139/v83-148
  17. Hunter, L.; Roberts, C.B. 145. The associating effect of the hydrogen atom. Part IX. The N–H–N bond. Virtual tautomerism of the formazyl compounds. J. Chem. Soc., 1941, 0(0), 820-823. doi: 10.1039/JR9410000820
  18. Abbas, A.A. New synthesis of 28- and 30- crown-formazans and Bis formazans. Tetrahedron, 1998, 54(40), 12421-12428. doi: 10.1016/S0040-4020(98)00761-3
  19. Khan, S.A.; Shahid, S.; Kanwal, S.; Hussain, G. Synthesis characterization and antibacterial activity of Cr (III), Co (III), Fe (II), Cu (II), Ni (III) complexes of 4-(2-(((2-hydroxy-5-nitrophenyl) diazenyl) (phenyl) methylene) hydrazinyl) benzene sulfonic acid based formazan dyes and their applications on leather. Dyes Pigments, 2018, 148, 31-43. doi: 10.1016/j.dyepig.2017.08.058
  20. Abdul Rahim, A.K. Metal complexes of formazans; Thesis. Department of Chemistry, University of Calicut, 2000.
  21. Tezcan, H. Synthesis and spectral properties of some bis-substituted formazans. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2008, 69(3), 971-979. doi: 10.1016/j.saa.2007.05.061 PMID: 17627872
  22. Bamoniri, A.; Mirjalili, B.B.F.; Moshtael-Arani, N. Nano BF3·SiO2: A green heterogeneous solid acid for synthesis of formazan dyes under solvent-free condition. J. Mol. Catal. Chem., 2014, 393, 272-278. doi: 10.1016/j.molcata.2014.06.024
  23. Shawali, A.S.; Samy, N.A. Functionalized formazans: A review on recent progress in their pharmacological activities. J. Adv. Res., 2015, 6(3), 241-254. doi: 10.1016/j.jare.2014.07.001 PMID: 26257923
  24. Desai, R.M.; Desai, J.M. Synthesis and antimicrobial activity of some new formazan derivatives. Indian J. Heterocycl. Chem., 1999, 8(4), 329-331.
  25. Zsoldos-Mády, V.; Pintér, I.; Peredy-Kajtár, M.; Perczel, A. Transformation of aldose formazans. Novel synthesis of 2-acetamido-2-deoxypentonolactones and a new pent-2-enose formazan. Carbohydr. Res., 2011, 346(12), 1534-1540. doi: 10.1016/j.carres.2011.04.026 PMID: 21592466
  26. Rama, A.; Nadendla, R.; Babu, N. Synthesis and Biological Evaluation of Some Novel Formazans. J. Pharm. Res., 2011, 4(1), 3.
  27. Saha, S.; Pal, D.; Kumar, S. Antifungal and Antibacterial Activities of Phenyl and Ortho-Hydroxy Phenyl Linked Imidazolyl Triazolo Hydroxamic Acid Derivatives. Inventi Rapid: Med. Chem., 2017, 2017(2), 42-49.
  28. Saharan, V.D.; Mahajan, S.S.; Mahajan, S. Development of gallic acid formazans as novel enoyl acyl carrier protein reductase inhibitors for the treatment of tuberculosis. Bioorg. Med. Chem. Lett., 2017, 27(4), 808-815. doi: 10.1016/j.bmcl.2017.01.026 PMID: 28117201
  29. Saha, S.; Banerjee, S.; Ganguly, S. Molecular Docking Studies of some Novel Hydroxamic Acid Derivatives. Int. J. Chemtech Res., 2010, 2(2), 932-936.
  30. Saha, S.; Pal, D.; Kumar, S. Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line. Trop. J. Pharm. Res., 2016, 15(7), 1401. doi: 10.4314/tjpr.v15i7.8
  31. Saha, S.; Yeom, G.S.; Nimse, S.B.; Pal, D. Combination Therapy of Ledipasvir and Itraconazole in the Treatment of COVID-19 Patients Coinfected with Black Fungus: An In Silico Statement. BioMed Res. Int., 2022, 2022, 1-10. doi: 10.1155/2022/5904261 PMID: 35463967
  32. Krishnan, V.; Verma, P.; Saha, S.; Singh, B.; Vinutha, T.; Kumar, R.R.; Kulshreshta, A.; Singh, S.P.; Sathyavathi, T.; Sachdev, A.; Praveen, S. Polyphenol-enriched extract from pearl millet (Pennisetum glaucum) inhibits key enzymes involved in post prandial hyper glycemia (α-amylase, α-glucosidase) and regulates hepatic glucose uptake. Biocatal. Agric. Biotechnol., 2022, 43102411. doi: 10.1016/j.bcab.2022.102411
  33. Joshi, B.C.; Juyal, V.; Sah, A.N.; Saha, S. Computational Investigation of Geniposidic Acid as an Anticancer Agent Using Molecular Docking, Molecular Dynamic Simulation, DFT Calculation, and OSIRIS-Molinspiration Profiling. Physical. Chem. Res., 2023, 11, 801-823.
  34. Kumari, R.; Kumar, R.; Lynn, A. g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model., 2014, 54(7), 1951-1962. doi: 10.1021/ci500020m PMID: 24850022
  35. Vishvakarma, V.K.; Singh, M.B.; Jain, P.; Kumari, K.; Singh, P. Hunting the main protease of SARS-CoV-2 by plitidepsin: Molecular docking and temperature-dependent molecular dynamics simulations. Amino Acids, 2022, 54(2), 205-213. doi: 10.1007/s00726-021-03098-1 PMID: 34807314
  36. Baker, N.A.; Sept, D.; Joseph, S.; Holst, M.J.; McCammon, J.A. Electrostatics of nanosystems: Application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA, 2001, 98(18), 10037-10041. doi: 10.1073/pnas.181342398 PMID: 11517324
  37. Bhardwaj, S.D.; Jolly, V.S. Synthesis, anti-HIV and anticancer activities of some new formazans. Asian J. Chem., 1997, 9, 48-51.
  38. Bhardwaj, S.D.; Phatak, P.; Jolly, V.S. Anti-cancer activity of Formazans. Orient. J. Chem., 1995, 2, 181-186.
  39. Mohammed, O.A.; Dahham, O.S. Synthesis, characterization, and study of antibacterial activity of some new formazan dyes derivatives, Derived from 2-mercapto benzoxazole. IOP Conf. Series: Materials Sci. & Engineering, 2018, 454, p. 012015.
  40. Desai, J.M.; Shah, V.H. Synthesis and antimicrobial profile of 5-imidazolinones, sulphonamides, azomethines, 2-azetidinones and formazans derived from 2-amino-3-cyano-5-(5-chloro-3-methyl-1-phenyl pyrazol-4-ylvinyl)-7,7-dimethyl-6,7-dihydro benzo thiophenes. Indian J. Chem., 2003, 42, 631-636.
  41. Pascua-Maestro, R.; Corraliza-Gomez, M.; Diez-Hermano, S.; Perez-Segurado, C.; Ganfornina, M.D.; Sanchez, D. The MTT-formazan assay: Complementary technical approaches and in vivo validation in Drosophila larvae. Acta Histochem., 2018, 120(3), 179-186. doi: 10.1016/j.acthis.2018.01.006 PMID: 29395318
  42. Journal, B.S.; Hassan, H.A.; Jinzeel, N.A. Synthesis of some heterocyclic compounds derived from 2-mercapto benzoxazole. Baghdad Sci J, 2013, 10(3), 766-778. doi: 10.21123/bsj.10.3.766-778
  43. Khalid, M.; Ali, A.; De la Torre, A.F.; Marrugo, K.P.; Concepcion, O.; Kamal, G.M.; Muhammad, S.; Al-Sehemi, A.G. Facile synthesis, spectral (ir, mass, uv−vis, nmr), linear and nonlinear investigation of the novel phosphonate compounds: a combined experimental and simulation study. Chem Sel., 2020, 5(10), 2994-3006. doi: 10.1002/slct.201904224
  44. Hussain, Z.; Yousif, E.; Ahmed, A.; Altaie, A. Synthesis and characterization of Schiff’s bases of sulfamethoxazole. Org. Med. Chem. Lett., 2014, 4(1), 1. doi: 10.1186/2191-2858-4-1 PMID: 24576663
  45. (45) Ericsson, H.M.; Sherris, J.C. Antibiotic sensitivity testing report of an international collaborative study. Acta Pathol. Microbiol. Scand., 1971, 1971, 217-223.
  46. Raviraj, R.; Jadhava, G.; Srikanth, B.; Harathic, P.; Shinde, G.P. Synthesis of some novel benzoxazole derivatives and their antimicrobial activity. J. Pharm. Res., 2011, 4(10), 3562-3565.
  47. Siddique, A.B.; Ahmad, S.; Shaheen, M.A.; Ali, A.; Tahir, M.N.; Vieira, L.C.; Muhammad, S.; Siddeeg, S.M. Synthesis, antimicrobial potential and computational studies of crystalline 4-bromo-2-(1,4,5-triphenyl-1 H -imidazole-2-yl)phenol and its metal complexes. Cryst Eng Comm, 2022, 24(47), 8237-8247. doi: 10.1039/D2CE01118B
  48. Khalid, M.; Ali, A.; Rehman, M.F.U.; Mustaqeem, M.; Ali, S.; Khan, M.U.; Asim, S.; Ahmad, N.; Saleem, M. Exploration of noncovalent interactions, chemical reactivity, and nonlinear optical properties of piperidone derivatives: a concise theoretical approach. ACS Omega, 2020, 5(22), 13236-13249. doi: 10.1021/acsomega.0c01273 PMID: 32548510
  49. Hussein, E.M.; Al-Rooqi, M.M.; Abd El-Galil, S.M.; Ahmed, S.A. Design, synthesis, and biological evaluation of novel N4-substituted sulfonamides: acetamides derivatives as dihydrofolate reductase (DHFR) inhibitors. BMC Chem., 2019, 13(1), 91. doi: 10.1186/s13065-019-0603-x PMID: 31384838
  50. Saha, S.; Pal, D.; Kumar, S. Hydroxyacetamide derivatives: cytotoxicity, genotoxicity, antioxidative and metal chelating studies. Indian J. Exp. Biol., 2017, 55, 831-837.
  51. Kushwaha, P.P.; Singh, A.K.; Bansal, T.; Yadav, A.; Prajapati, K.S.; Shuaib, M.; Kumar, S. Identification of natural inhibitors against sars-cov-2 drugable targets using molecular docking, molecular dynamics simulation, and mm-pbsa approach. Front. Cell. Infect. Microbiol., 2021, 11730288. doi: 10.3389/fcimb.2021.730288 PMID: 34458164
  52. Vishvakarma, V.K.; Pal, S.; Singh, P.; Bahadur, I. Interactions between main protease of SARS-CoV-2 and testosterone or progesterone using computational approach. J. Mol. Struct., 2022, 1251131965. doi: 10.1016/j.molstruc.2021.131965 PMID: 34840349
  53. Jin, R.Y.; Zeng, C.Y.; Liang, X.H.; Sun, X.H.; Liu, Y.F.; Wang, Y.Y.; Zhou, S. Design, synthesis, biological activities and DFT calculation of novel 1,2,4-triazole Schiff base derivatives. Bioorg. Chem., 2018, 80, 253-260. doi: 10.1016/j.bioorg.2018.06.030 PMID: 29966871
  54. Alhassan, A.M.; Ahmed, Q.U.; Malami, I.; Zakaria, Z.A. Pseudocedrela kotschyi: a review of ethnomedicinal uses, pharmacology and phytochemistry. Pharm. Biol., 2021, 59(1), 953-961. doi: 10.1080/13880209.2021.1950776 PMID: 34283002
  55. Zinad, D.S.; Mahal, A.; Salman, G.A.; Shareef, O.A.; Pratama, M.R.F. Molecular docking and DFT study of synthesized oxazine derivatives. Egypt. J. Chem., 2022, 65(7), 231-240.
  56. Saleem, T.; Khan, S.; Yaqub, M.; Khalid, M.; Islam, M.; Yousaf ur Rehman, M.; Rashid, M.; Shafiq, I.; Braga, A.A.C.; Syed, A.; Bahkali, A.H.; Trant, J.F.; Shafiq, Z. Novel quinoline-derived chemosensors: synthesis, anion recognition, spectroscopic, and computational study. New J. Chem., 2022, 46(38), 18233-18243. doi: 10.1039/D2NJ02666J
  57. Khalid, M.; Ahmed, R.; shafiq, I.; Arshad, M.; Asghar, M.A.; Munawar, K.S.; Imran, M.; Braga, A.A.C. First theoretical framework for highly efficient photovoltaic parameters by structural modification with benzothiophene-incorporated acceptors in dithiophene based chromophores. Sci. Rep., 2022, 12(1), 20148. doi: 10.1038/s41598-022-24087-8 PMID: 36418911
  58. Arshad, M.N.; Shafiq, I.; Khalid, M.; Asad, M.; Asiri, A.M.; Alotaibi, M.M.; Braga, A.A.C.; Khan, A.; Alamry, K.A. Enhancing the photovoltaic properties via incorporation of selenophene units in organic chromophores with A2-π2-A1-π1-A2 configuration: A DFT-based exploration. Polymers, 2023, 15(6), 1508. doi: 10.3390/polym15061508 PMID: 36987288
  59. Concepcion, O.; Ali, A.; Khalid, M.; F de la Torre, A.; Khan, M.U.; Raza, A.R.; Kamal, G.M.; Rehman, M.F.U.; Alam, M.M.; Imran, M.; Braga, A.A.C.; Pertino, M.W. Facile synthesis of diversely functionalized peptoids, spectroscopic characterization, and dft-based nonlinear optical exploration. ACS Omega, 2021, 6(40), 26016-26025. doi: 10.1021/acsomega.1c02962 PMID: 34660963
  60. Khalid, M.; Khan, M.U.; Shafiq, I.; Hussain, R.; Ali, A.; Imran, M.; Braga, A.A.C.; Fayyaz ur Rehman, M.; Akram, M.S. Structural modulation of π-conjugated linkers in D–π–A dyes based on triphenylamine dicyanovinylene framework to explore the NLO properties. R. Soc. Open Sci., 2021, 8(8), 210570. doi: 10.1098/rsos.210570
  61. Akhter, S.; Concepcion, O.; de la Torre, A.F.; Ali, A.; Raza, A.R.; Eman, R.; Khalid, M.; Rehman, M.F.; Akram, M.S.; Ali, H.M. Synthesis, spectroscopic characterization, DFT and molecular dynamics of quinoline-based peptoids. Arab. J. Chem., 2023, 16(4), 104570. doi: 10.1016/j.arabjc.2023.104570

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers