Design, structual inspection, pharmaceutical and interaction with DNA studies of some transition metal chelates derived from ciprofloxacin /
تصميم وفحص الشكل التركيبي ودراسات صيدلانية والتداخل مع الحمض النووي الديؤكسي ريبوزي لبعض مخلبيات العناصر الانتقاليه والمشتقه من السيبروفلوكساسين
by Yasser Abo Elfotoh Elsayed ; Supervisors Prof.Dr.Gehad Genidy Mohamed, Prof.Dr.Ahmed Mohammed Abu-Dief.
- 164 pages : illustrations ; 25 cm. + CD.
Thesis (M.Sc)-Cairo University, 2024.
Bibliography: pages 144-163.
Novel compounds with pharmacological activity were synthesized from Pd [II], Fe [III], Cr [II], Ni [II] and Cu [II] ions with 1_Cyclopropyl _ 6- fluoro_ 4_ (2-hydroxy-phenylimino)_7_ piperazin _1_yl_1,4_dihydro_quinoline_ 3_ carboxylic acid (CFAP). The ligand's NH and OH groups allowed it to interact with the metals as a neutral tri-dentate. The novel compounds were described using (1H and 13C NMR spectra),( FT- IR spectrums), (TGA), ultraviolet _ visible light), (conductance of molecules), and CHN-analysis. Additionally, the pH profile of the CFAP complexes indicated great stability, and the complexes' stability constant was discovered in the solution. To extract important properties for CFAP and its complexes, computational research was used CFAPCu , CFAPCr, CFAPNi, and CFAPFe have octahedral geometry, while CFAPPd has square planar geometry. To investigate the molecular geometry, density functional theory calculations (DFT) were carried out. The molar ratio and continuous fluctuation data confirmed that the (M:L) ratio was (1:1). In vitro tests were conducted to evaluate schiff base's antimicrobial action ligand and its metal chelates against fungal and bacterial infections. The findings showed that the antimicrobial efficacy is as follows: when CFAPPd is compared to Fluconazol and Ofloxacin as reference medications, it is the highly inhibitor complex. The novel The ligands and their complexes in vitro carcinogenic potential in opposition to the [ Hep_G2 , MCF_7 , and HCT_116 ] cell lines was also studied. As compared to the medication vinblastine, the results once again demonstrated that CFAPPd is the most active agent. Moreover, the complexes demonstrated strong reactivity in capturing free radicals when their antioxidant activity was investigated. Viscosity, spectral investigations, and gel electrophoreses were used to identify the interaction between metal chelates and DNA. Every examined
compound is shown to be an enthusiastic DNA binder by viscosity and spectrophotometric titration investigations. The heightened hydrophobic and electrostatic interactions between aromatic rings could be the cause of this. Ultimately, these compounds could be regarded as promising bioactive substances. Novel compounds with pharmacological activity were synthesized from Pd(II), Fe(III), Cr(III), Ni(II) and Cu(II) ions with 4-[2-(3-Carboxy-1- cyclopropyl-6-fluoro-7-piperazin-1-yl-2,3-dihydro-1H-quinolin-4- ylideneamino)-phenylimino]-1-cyclopropyl-6-fluoro-7-piperazin-1-yl-1,4- dihydro-quinoline-3-carboxylic acid (CFPD). The newly synthesized compounds have been investigated by 1H- and 13C-NMR spectra, FT-IR spectra, CHN analyses, TG, UV-Vis, and molar conductivity. In addition, the pH-profile of the CFPD complexes showed remarkable stability, and a stability constant was identified in solution. To extract significant characteristics for CFPD and its complexes and to investigate the molecular geometry, computational analysis occurred. Through its NH and OH groups, the ligand interacted with the metal ions as a neutral bidentate that formed CFPD-Pd(II) complex has square planar geometry, CFPD-Cu(II), CFPD- Cr(III), CFPD-Ni(II) and CFPD-Fe(III) complexes have octahedral geometry. The (M:L) ratio of 1:1 was shown by the results of the molar ratio and continuous variation procedures. A variety of fungi and viral pathogens were used to investigate the in vitro antibacterial activity of the Schiff base ligand and its complexes with metals. The results revealed that the antimicrobial efficacy followed the order: CFPD-Pd(II) complex is the highly inhibitor complex compared to fluconazol and ofloxacin as reference drugs. The in-vitro cytotoxic activity of the new ligand and its complexes was also investigated against Hep-G2, MCF-7 and HCT-116 cell lines. The results showed again that CFPD-Pd(II) complex is the highest active agent
compared to vinblastine drug. In addition, the complexes showed high reactivity in catching free radicals when their antioxidant activity was examined. By the application of viscosity, spectrum analysis, and gel electrophoreses, the interaction among metal chelates and DNA was determined. Studies on viscosity and spectrophotometric titration showed that every substance in test is a strong DNA binder. Increased hydrophobic and electrostatic interactions between aromatic rings could be the cause of this. In conclusion, these complexes have the potential to be effective bioactive agents. تعتبر مركبات الفلوروكينولين من المركبات الكيميائية الهامة والتى تلعب دوراً مميزاً فى مجال الكيمياء التناسقية وذلك لقدرتها على تكوين متراكبات مستقرة بسهولة مع كثير من أيونات العناصر الإنتقالية بالإضافة إلى ذلك ترجع أهميتها لكونها تستخدم كمضادات للبكتريا والفطريات، كما أنها لها قدرة فائقة علي الارتباط مع الحمض النووي الديؤكسي ريبوزي مما يؤهلها لأن تستخدم كمضادات قوية للفيروسات والأورام السرطانية وكذلك لقدرتها على إقتناص أيونات المعادن مما يجعل لها دورا هاما فى الكيمياء التحليلية والصناعية حيث أنها تستخدم فى تنقية مياه الشرب وتخليصها من أيونات المعادن الثقيلة وكذلك تستخدم لمقاومة تاكل المعادن مثل الحديد. واجتذب سيبروفلوكساسين أيضًا اهتمامًا من المجتمع العلمي بسبب نشاطه في موت الخلايا المبرمج ومضاد التكاثر في العديد من خطوط السرطان.
وبناءا على ما سبق ذكره فإن الأهداف الرئيسية من هذه الرسالة جاءت علي النحو التالي: • تحضير بعض ليجيندات الإيمين المحتوية على السيبروفلوكساسين ثلاثية ورباعية العطاء • تحضير المتراكبات مع بعض أيونات العناصر الإنتقالية ثنائية التكافؤ مثل Pd(II), Ni(II) and Cu(II) وثلاثية التكافؤ مثل Fe(III), Cr(III), والتى ثبت ان لها فاعلية بيولوجية ضد العديد من الخلايا البكتيرية والفطريات والخلايا السرطانية والشقوق الحرة.
Text in English and abstract in Arabic & English.
Inorganic
Schiff base complexes Thermal analyses (TG and DTG) DFT antibacterial activity antioxidant activity Molecular docking studies.