OpenLB
Open Library of Bioscience
Advanced Search
Molecular diversity
Oct 02, 2024;

Design, synthesis, and computational analysis (molecular docking, DFT, MEP, RDG, ELF) of diazepine and oxazepine sulfonamides: biological evaluation for in vitro and in vivo anti-inflammatory, antimicrobial, and cytotoxicity predictions.

Sangar Ali Hassan, Dara Muhammed Aziz, Dana Ali Kader, Shwana Muhamad Rasul, Meer Ali Muhamad, Alla Ahmad Muhammedamin
Author Information
  1. Sangar Ali Hassan: Department of Chemistry, College of Sciences, University of Raparin, Kurdistan Regional Government, Main Street, Ranyah, 46012, Iraq.
  2. Dara Muhammed Aziz: Department of Chemistry, College of Sciences, University of Raparin, Kurdistan Regional Government, Main Street, Ranyah, 46012, Iraq. darachem@uor.edu.krd.
  3. Dana Ali Kader: Department of Chemistry, College of Education, University of Sulaimani, Old Campus, Sulaymaniyah, 46001, Kurdistan Region, Iraq.
  4. Shwana Muhamad Rasul: Department of Chemistry, College of Sciences, University of Raparin, Kurdistan Regional Government, Main Street, Ranyah, 46012, Iraq.
  5. Meer Ali Muhamad: Department of Chemistry, College of Sciences, University of Raparin, Kurdistan Regional Government, Main Street, Ranyah, 46012, Iraq.
  6. Alla Ahmad Muhammedamin: Department of Chemistry, College of Sciences, University of Raparin, Kurdistan Regional Government, Main Street, Ranyah, 46012, Iraq.
PMID: 39356365 DOI: 10.1007/s11030-024-10996-5

Abstract

We report the synthesis and extensive characterization of Diazepane and Oxazepane derivatives, followed by their biological evaluation. These compounds were assessed for in vitro and in vivo antimicrobial, anti-inflammatory, and anticancer activities. Among the synthesized molecules, compound 5b demonstrated remarkable antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis with MIC values of 20 and 40 ��g/mL, respectively. Additionally, 5b exhibited potent anti-inflammatory effects both in vitro and in vivo. Advanced computational studies, including DFT, MEP, RDG, and ELF analyses, were performed to understand the electronic distribution and molecular interactions. The bioactivity and physicochemical properties of these derivatives were further predicted using PASS and pkCSM platforms, emphasizing their potential as promising lead molecules in drug development.

Keywords

Anti-inflammatory Antimicrobial DFT Diazepane ELF Molecular docking Oxazepane RDG

References

  1. Soni J, Sinha S, Pandey R (2024) Understanding bacterial pathogenicity: a closer look at the journey of harmful microbes. Front Microbiol 15:1370818 [PMID: 38444801]
  2. Jiang Q et al (2019) Quorum sensing: a prospective therapeutic target for bacterial diseases. BioMed Res Int 2019:1���15
  3. Kiriiri GK, Njogu PM, Mwangi AN (2020) Exploring different approaches to improve the success of drug discovery and development projects: a review. Future J Pharm Sci 6:1���12
  4. Hassan SA, Aziz DM (2022) An efficient one-pot three-component synthesis, molecular docking, ADME and DFT predictions of new series thiazolidin-4-one derivatives bearing a sulfonamide moiety as potential antimicrobial and antioxidant agents. Egypt J Chem 65(8):133���146
  5. Hassan SA, Aziz DM (2021) Synthesis of new series bis-3-chloro-��-lactam derivatives from symmetrical bis-Schiff bases as effective antimicrobial agents with molecular docking studies. Sci J Univ Zakho 9(3):128���137 [DOI: 10.25271/sjuoz.2021.9.3.830]
  6. Hassan SA, Aziz DM (2021) Synthesis, in vitro antimicrobial assay and molecular docking studies of some new symmetrical bis-Schiff bases and their 2-azetidinones. Zanco J Pure Appl Sci. https://doi.org/10.21271/ZJPAS.33.2.4 [DOI: 10.21271/ZJPAS.33.2.4]
  7. Aziz DM, Azeez HJ (2020) Synthesis of new ��-lactam-N-(thiazol-2-yl) benzene sulfonamide hybrids: their in vitro antimicrobial and in silico molecular docking studies. J Mol Struct 1222:128904 [DOI: 10.1016/j.molstruc.2020.128904]
  8. Psomas G, Kessissoglou DP (2013) Quinolones and non-steroidal anti-inflammatory drugs interacting with copper (II), nickel (II), cobalt (II) and zinc (II): structural features, biological evaluation and perspectives. Dalton Trans 42(18):6252���6276 [PMID: 23529676]
  9. Sousa SM et al (2023) Repurposing some of the well-known Non-steroid Anti-inflammatory Drugs (NSAIDs) for cancer treatment. Curr Top Med Chem 23(13):1171���1195 [PMID: 36717997]
  10. Le��niewska A, Przybylski P (2024) Seven-membered N-heterocycles as approved drugs and promising leads in medicinal chemistry as well as the metal-free domino access to their scaffolds. Eur J Med Chem 275:116556 [PMID: 38879971]
  11. Tshinavhe R (2021) Design, synthesis and anti-Tb evaluation of 6 dialkylaminopyrimidine carboxamides. University of Johannesburg, South Africa
  12. Al-Mulla A (2017) A review: biological importance of heterocyclic compounds. Der Pharma Chemica 9(13):141���147
  13. Dze KC, Samad F (2020) Heterocycles, their synthesis and industrial applications: a review. Int J Appl Sci Eng Technol 8:36���56
  14. Adarve-Cardona L, Garay-Talero A, Gamba-S��nchez D (2023) Synthesis of naturally occurring seven-membered nitrogen heterocycles and related bioactive compounds. Stud Nat Prod Chem 78:189���235 [DOI: 10.1016/B978-0-323-91253-2.00016-9]
  15. Akter M, Rupa K, Anbarasan P (2022) 1, 2, 3-Triazole and its analogues: New surrogates for diazo compounds. Chem Rev 122(15):13108���13205 [PMID: 35852917]
  16. Gomha S et al (2016) Ecofriendly one-pot synthesis and antiviral evaluation of novel pyrazolyl pyrazolines of medicinal interest. Turk J Chem 40(3):484���498 [DOI: 10.3906/kim-1510-25]
  17. Muhammad FM, Khairallah BA, Albadrany K (2024) Synthesis, characterization and antibacterial evaluation of novel 1, 3-oxazepine derivatives using a cycloaddition approach. J Angiother 8(3):1���5
  18. Kaur N et al (2020) Photochemical C���N bond forming reactions for the synthesis of five-membered fused N-heterocycles. Synth Commun 50(9):1286���1334 [DOI: 10.1080/00397911.2020.1713378]
  19. Kshash AH (2020) Synthesis and characterization of tetrachloro-1, 3-oxazepine derivatives and evaluation of their biological activities. Acta Chim Slov 67(1):113���118 [PMID: 33558920]
  20. Khalil MI (2021) Synthesis and characterization of new oxazepine compounds derived from guanine. Mater. Today: Proc 45:4960���4963
  21. Al Garadi W et al (2022) 4-phenyl-decahydro-1H-1, 5-benzodiazepin-2-one as novel and effective corrosion inhibitor for carbon steel in 1 M HCl solution: a combined experimental and empirical studies. J Indian Chem Soc 99(11):100742 [DOI: 10.1016/j.jics.2022.100742]
  22. Malki Y, Martinez J, Masurier N (2021) 1, 3-diazepine: a privileged scaffold in medicinal chemistry. Med Res Rev 41(4):2247���2315 [PMID: 33645848]
  23. Knabe J, B��ch HP, Bender S (1995) 1, 5���Benzodiazepine, 2. Mitt.: Entgegengesetzte zentralnerv��se Wirkungen der Enantiomere von zwei 3, 3���dialkyl���1, 5���benzodiazepin���2, 4���dionen. Archiv der Pharmazie 328(1): 59���66
  24. Sato Y et al (2020) Associations of benzodiazepine with adverse prognosis in heart failure patients with insomnia. J Am Heart Assoc 9(7):e013982 [PMID: 32200713]
  25. Shaabani S et al (2019) A one-pot synthesis of oxazepine-quinazolinone bis-heterocyclic scaffolds via isocyanide-based three-component reactions. Front Chem 7:623 [PMID: 31620422]
  26. Hayes BL (2004) Recent advances in microwave-assisted synthesis. Aldrichimica Acta 37(2):66���77
  27. Hassan SA (2019) Synthesis, spectroscopic study and biological activity of some new heterocyclic compounds derived from sulfadiazine. Zanco J Pure Appl Sci. https://doi.org/10.21271/ZJPAS.31.6.10 [DOI: 10.21271/ZJPAS.31.6.10]
  28. Hassan SA et al (2023) Design and synthesis of oxazepine derivatives from sulfonamide Schiff bases as antimicrobial and antioxidant agents with low cytotoxicity and hemolytic prospective. J Mol Struct 1292:136121 [DOI: 10.1016/j.molstruc.2023.136121]
  29. Adam R, Zimam EH (2014) Synthesis, characterization and study biological activity of some new 1, 3-oxazepine and 1, 3-diazepine derivatives. Karbala J Pharm Sci 5(7):195���217
  30. Agar M-H (2006) Phenotypic detection of methicillin. J Clin Microbiol 16:4395���4399
  31. Wallace RJ Jr, Dalovisio J, Pankey G (1979) Disk diffusion testing of susceptibility of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents. Antimicrob Agents Chemother 16(5):611���614 [PMID: 526002]
  32. Gaines C et al (2013) Development of a porcine deep partial thickness burn model. Burns 39(2):311���319 [PMID: 22981797]
  33. Pereira DdST et al (2012) Development of animal model for studying deep second-degree thermal burns. J Biomed Biotechnol 2012
  34. Samad MK, Hawaiz FE (2019) Synthesis, characterization, antioxidant power and acute toxicity of some new azo-benzamide and azo-imidazolone derivatives with in vivo and in vitro antimicrobial evaluation. Bioorg Chem 85:431���444 [PMID: 30685693]
  35. Gandhidasan R, Thamaraichelvan A, Baburaj S (1991) Anti-inflammatory action of Lannea coromandelica by HRBC membrane stabilization
  36. Li X et al (2014) Functional gold nanoparticles as potent antimicrobial agents against multi-drug-resistant bacteria. ACS Nano 8(10):10682���10686 [PMID: 25232643]
  37. Lu Y et al (2018) Construction of a molecular structure model of mild-oxidized Chinese lignite using Gaussian09 based on data from FTIR, solid state 13 C-NMR. J Mol Model 24:1���7 [DOI: 10.1007/s00894-018-3677-9]
  38. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(1):33���38 [PMID: 8744570]
  39. Lu T, Chen F (2012) Multiwfn: a multifunctional wave function analyzer. J Comput Chem 33(5):580���592 [PMID: 22162017]
  40. Khan MF et al (2020) Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism. Biomed Pharmacother 131:110774 [PMID: 33152933]
  41. Pires DE, Blundell TL, Ascher DB (2015) pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J Med Chem 58(9):4066���4072 [PMID: 25860834]
  42. Kader DA et al (2024) Green synthesis of ZnO/catechin nanocomposite: comprehensive characterization, optical study, computational analysis, biological applications and molecular docking. Mater Chem Phys 319:129408 [DOI: 10.1016/j.matchemphys.2024.129408]
  43. Aziz DM, Hassan SA, Hamad OQ (2023) Azo-azomethine complex activity and sensor potential toward Ca (II) ion in life samples: the spectroscopic and morphological studies. J Mol Struct 1293:136204 [DOI: 10.1016/j.molstruc.2023.136204]
  44. Rezvan VH, Afsaneh A (2024) Green synthesis of a novel bis-Schiff base derived from 4-N, N-dimethylaminobenzaldehyde and hexamethylenediamine: DFT study. J Mol Struct 1313:138744 [DOI: 10.1016/j.molstruc.2024.138744]
  45. Muhammed Aziz D et al (2023) New azo-azomethine derivatives: synthesis, characterization, computational, solvatochromic UV���Vis absorption and antibacterial studies. J Mol Struct 1284:135451 [DOI: 10.1016/j.molstruc.2023.135451]
  46. Mushtaq A et al (2021) Mechanisms of action of antibacterial agents. Practical handbook of microbiology. CRC Press, pp 747���776 [DOI: 10.1201/9781003099277-54]
  47. Carvalho SM et al (2022) Defenses of multidrug resistant pathogens against reactive nitrogen species produced in infected hosts. Adv Microb Physiol 80:85���155 [PMID: 35489794]
  48. Modak B et al (2022) Mycobacterial membranes as actionable targets for lipid-centric therapy in tuberculosis. J Med Chem 65(4):3046���3065 [PMID: 35133820]
  49. Abd El-Aleam RH et al (2021) Bacterial virulence factors: a target for heterocyclic compounds to combat bacterial resistance. RSC Adv 11(58):36459���36482 [PMID: 35494393]
  50. El-Wakil MH, Meheissen MA, Abu-Serie MM (2021) Nitrofurazone repurposing towards design and synthesis of novel apoptotic-dependent anticancer and antimicrobial agents: biological evaluation, kinetic studies and molecular modeling. Bioorg Chem 113:104971 [PMID: 34051413]
  51. Odusami JA et al (2020) Synthesis of substituted N-(2���-nitrophenyl) pyrrolidine-2-carboxamides towards the design of proline-rich antimicrobial peptide mimics to eliminate bacterial resistance to antibiotics. Bioorg Chem 105:104340 [PMID: 33096308]
  52. Schilf W, Kamie��ski B, U��arevi�� K (2013) Nitrogen and carbon CPMAS NMR investigations of keto���enol tautomerism in asymmetric o-hydroxy Schiff bases. J Mol Struct 1031:211���215 [DOI: 10.1016/j.molstruc.2012.10.004]
  53. Nagasundaram N et al (2022) Ultrasound promoted synthesis of new azo fused dihydropyrano [2, 3-c] pyrazole derivatives: In vitro antimicrobial, anticancer, DFT, in silico ADMET and molecular docking studies. J Mol Struct 1263:133091 [DOI: 10.1016/j.molstruc.2022.133091]
  54. Li C-H et al (2022) Design, synthesis, and biological evaluation of dinuclear bismuth (III) complexes with Isoniazid-derived Schiff bases. J Inorg Biochem 235:111931 [PMID: 35868066]
  55. Clarke LA, Hollak CE (2015) The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders. Best Pract Res Clin Endocrinol Metab 29(2):219���235 [PMID: 25987175]
  56. Enechi OC et al (2022) Phytochemical composition and anti-inflammatory potential of flavonoid-rich fraction of Erythrina senegalensis DC (Fabaceae) leaf. Trop J Nat Prod Res 6(9):1511���1514 [DOI: 10.26538/tjnpr/v6i9.29]
  57. R��cker H-M (2015) Characterization of the anti-inflammatory activity of enones based on the evaluation of their heme oxygenase-1 and inducible NO synthase activity
  58. Sava A (2021) Design, synthesis and biological evaluation of novel anti-inflammatory agents. Universit�� d���Orl��ans; Universitatea de medicina si farmacie, Grigore T. Popa
  59. Varala R et al (2024) Iodoxybenzoic acid (IBX) in organic synthesis: a septennial review. Curr Org Synth 21(5):607���664 [PMID: 37861006]
  60. Alebachew T et al (2012) Staphylococcus aureus burn wound infection among patients attending Yekatit 12 hospital burn unit, Addis Ababa, Ethiopia. Ethiopian J Health Sci 22(3)
  61. MCPS F (2012) Bacterial profile of burn wound infections in burn patients. Ann Pak Inst Med Sci 8(1): 54���57
  62. Yolba�� �� et al (2013) Common pathogens isolated from burn wounds and their antibiotic resistance patterns. Dicle Med J 40(3):364���368 [DOI: 10.5798/diclemedj.0921.2013.03.0290]
  63. Aziz DM et al (2023) A synergistic investigation of azo-thiazole derivatives incorporating thiazole moieties: a comprehensive exploration of their synthesis, characterization, computational insights, solvatochromism, and multimodal biological activity assessment. RSC Adv 13(49):34534���34555 [PMID: 38024963]
  64. G��zquez JL (1998) A hardness and softness theory of bond energies and chemical reactivity. Theoretical and computational chemistry. Elsevier, pp 135���152
  65. Ntui TN et al (2023) Synthesis, spectroscopic, DFT study, and molecular modeling of thiophene-carbonitrile against enoyl-ACP reductase receptor. Chemistry Africa 6(2):945���966 [DOI: 10.1007/s42250-022-00544-9]
  66. Zhang C et al (2022) Inter-/intra-molecular interactions, preferential solvation, and dissolution and transfer property for tirofiban in aqueous co-solvent mixtures. J Mol Liq 361:119665 [DOI: 10.1016/j.molliq.2022.119665]
  67. Dexlin XD et al (2021) Synthesis and DFT computations on structural, electronic and vibrational spectra, RDG analysis and molecular docking of novel anti COVID-19 molecule 3, 5 dimethyl pyrazolium 3, 5 dichloro salicylate. J Mol Struct 1246:131165 [PMID: 36532120]
  68. Morris GM et al (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19(14):1639���1662 [DOI: 10.1002/(SICI)1096-987X(19981115)19]
Journal Article

Word Cloud

Created with Highcharts 10.0.0vitrovivoanti-inflammatoryDFTRDGELFsynthesisDiazepaneOxazepanederivativesbiologicalevaluationantimicrobialmolecules5bStaphylococcuscomputationalMEPmoleculardockingreportextensivecharacterizationfollowedcompoundsassessedanticanceractivitiesAmongsynthesizedcompounddemonstratedremarkableantibacterialactivityaureusepidermidisMICvalues2040��g/mLrespectivelyAdditionallyexhibitedpotenteffectsAdvancedstudiesincludinganalysesperformedunderstandelectronicdistributioninteractionsbioactivityphysicochemicalpropertiespredictedusingPASSpkCSMplatformsemphasizingpotentialpromisingleaddrugdevelopmentDesignanalysisdiazepineoxazepinesulfonamides:cytotoxicitypredictionsAnti-inflammatoryAntimicrobialMolecular

Similar Articles

Cited By