Rukhsana Gul

Preliminary investigation of anticancer activity by determining the DNA binding and antioxidant potency of new ferrocene incorporated N,N',N″-trisubstituted phenylguanidines.

Six new bioactive ferrocene based phenylguanidines were successively synthesized and characterized by means of various analytical techniques like elemental analysis, FT-IR, multinuclear ((1)H and (13)C) NMR, UV-Vis spectroscopy and cyclic voltammetry. The interaction of compounds with DNA was investigated by spectroscopic and cyclic voltammetric measurements. The interaction was found to be the electrostatic and the binding constants values were impressively larger. Compounds f-1, f-2, f-3 have slight larger binding constant values ranging from 0.8×10(5) to 2.4×10(5) as compared to g-1, g-2 and g-3 ranging from 7.6×10(4) to 1.1×10(5) which is most probably due to the presence of ferrocene at para position where the delocalization of electrons is maximum. Antioxidant activity was determined by UV-Vis spectrophotometer by using DPPH as a free radical. All the compounds exhibit good antioxidant activity and the results so obtained support the structure activity relationship.

New supramolecular ferrocenyl phenylguanidines as potent antimicrobial and DNA-binding agents

Six new ferrocenyl phenylguanidines have been synthesized and characterized by elemental analysis, FT-IR, multinuclear (1H and 13C) NMR, and single crystal analysis. The latter showed a supramolecular structure for 2 mediated by O H and π H interactions. A subsequent DNA-binding study of these complexes proved them to be good DNA binders with the binding constant varying in the range of 1.2–5.6 × 105 M−1. These compounds were found to have moderate antibacterial and significant antifungal activities, especially for compounds having a chlorophenyl. These compounds may emerge as a new class of anticancer and antifungal agents alone or in combination with other drugs.

New natural urease inhibitors from Ranunculus repens

Phytochemical investigations on the chloroform and ethyl acetate soluble fractions of the roots of Ranunculus repens led to the isolation of methyl 3,4,5-trihydroxybenzoate 1, R(+)- 4-methoxydalbergione 2 and R(+)-dalbergiophenol 3. The structures of these compounds were established through spectral studies including 1D and 2D NMR experiments and by comparison with literature data. These compounds showed potent inhibitory activity against urease.

Biologically Active New N, N', N''-Tri-Substituted Ferrocenyl Phenylguanidines and their Characterization.

BACKGROUND Introducing new candidates for various biological targets is a prime characteristic of the present day medicinal research and development. Guanidines are the important bioactive compounds and are well recognized for their diverse biological activities, especially as anticancer, antimicrobial and antioxidant agents. Due to the favorable electronic properties of ferrocene like lipophilicity, redox activity, stability in solution state and its easy derivatization, have made ferrocenyl compounds very popular molecules for biological uses. OBJECTIVES Keeping in sight, it is valuable to synthesize ferrocenyl guanidines to increase the binding potency with DNA, make them redox active and more lipophilic compounds. METHODS Six new ferrocenyl phenylguanidines (F1 - F6) have been synthesized via multi step protocol. The structures of F1 - F6 were established by using elemental analysis, UV-visible, multinuclear (1H and 13C) NMR and FTIR spectroscopy. Solution phase redox behavior, of the synthesized compounds, has been characterized by cyclic voltammetry. Two compounds (F2 & F4) were characterized by single crystal XRD. RESULTS Due to the biological importance of guanidines; these ferrocenyl guanidiens were screened for different biological activities like antibacterial, antifungal, antioxidant and DNA binding. DNA interaction study was done by using UV-visible spectrometry and cyclic voltammetry revealed good binding capacity of the test compounds. CONCLUSION The results revealed that the ferrocene incorporation to guanidines enhances their DNA binding ability. A similar trend was found in antioxidant and antimicrobial studies. Being the bioactive molecules these compounds are potential drug candidates.

Xanthine oxidase inhibiting compounds from Ranunculus repens

The genus Ranunculus belongs to the family Ranunculaceae, which comprises 50 genera and 2000 species. In Pakistan, it is represented by 22 genera and 114 species. The phytochemical studies on various species of genus Ranunculus have reported that they contain anemone [1], carotene [2], flavone-glycosides [3], and ranuncosides [4]. The saline extracts of some species have been reported to possess anti-bacterial, anti-fungal, and anti-malarial activities [5–7]. Ranunculus repens L. is widely distributed in the northern areas of Pakistan and is used for medicinal purposes [8]. Several genera in this family possess ir ritant properties due to the presence of protoanemonin [9, 10]. The protoanemonin also inhibits mitosis in plant cells [11]. No work has been reported so far on this species. The diverse medicinal uses attributed to this species prompted us to carry out phytochemical and biological studies on this plant. Biological screening of the methanolic extract revealed significant inhibit ory activity against the enzyme xanthine oxidase [12]. On fractionation, the major inhibitory activity against this enzyme was detected in the chloroform soluble fraction. The chloroform soluble fraction resulted in the isolation and structure elucidatio n of R(+)-dalbergiphenol ( 1), R(+)-4-methoxydalbergione ( 2), and methyl-3,4,5-trihydroxybenzoate ( 3). All of them have been reported for the first time from this plant.

2-(3-Chloro-benzo-yl)-3-(3,4-di-chloro-phen-yl)-1-(4-ferrocenylphen-yl)guanidine.

In the title compound, [Fe(C5H5)(C25H17Cl3N3O)], the isolated cyclopentadienyl (Cp) ring is disordered over two set of sites in a 0.577 (8):0.423 (8) ratio. The dihedral angle between the other Cp ring and its attached benzene ring is 13.6 (3)°, and that between the benzene ring and the guanidine group is 64.8 (2)°. One of the N—H groups forms both an intra- and an intermolecular N—H⋯O hydrogen bond; the other N—H group does not form any hydrogen bonds. In the crystal, pairs of the intermolecular N—H⋯O hydrogen bonds link the molecules into inversion dimers.

Synthesis and functionalization of chitosan built hydrogel with induced hydrophilicity for extended release of sparingly soluble drugs

Abstract Addressing the functional biomaterials as next-generation therapeutics, chitosan and alginic acid were copolymerized in the form of chemically crosslinked interpenetrating networks (IPNs). The native hydrogel was functionalized via carbodiimide (EDC), catalyzed coupling of soft ligand (1,2-Ethylenediamine) and hard ligand (4-aminophenol) to replace –OH groups in alginic acid units for extended hydrogel- interfaces with the aqueous and sparingly soluble drug solutions. The chemical structure, Lower solution critical temperature (LCST ≈ 37.88 °C), particle size (Zh,app ≈ 150–200 nm), grain size (160–360 nm), surface roughness (85–250 nm), conductivity (37–74 mv) and zeta potential (16–32 mv) of native and functionalized hydrogel were investigated by using FT-IR, solid state-13C-NMR, TGA, DSC, FESEM, AFM and dynamic light scattering (DLS) measurements. The effective swelling, drug loading (47–78%) and drug release (53–86%) profiles were adjusted based on selective functionalization of hydrophobic IPNs due to electrostatic complexation and extended interactions of hydrophilic ligands with the aqueous and drug solutions. Drug release from the hydrogel matrices with diffusion coefficient n ≈ 0.7 was established by Non- Fickian diffusion mechanism. In vitro degradation trials of the hydrogel with a 20% loss of wet mass in simulated gastric fluid (SGF) and 38% loss of wet mass in simulated intestinal fluid (SIF), were investigated for 400 h through bulk erosion. Consequently, a slower rate of drug loading and release was observed for native hydrogel, due to stronger H-bonding, interlocking and entanglement within the IPNs, which was finely tuned and extended by the induced hydrophilic and functional ligands. In the light of induced hydrophilicity, such functional hydrogel could be highly attractive for extended release of sparingly soluble drugs.

New ferrocenyl guanidines as potent antioxidants, protein kinase inhibitors and cytotoxic agents against human leukemia THP-1 cell line

Six new ferrocenyl guanidines were synthesized and characterized by elemental analysis, FT-IR and 1H and 13C NMR. Compounds 1–6 were screened for antioxidant, protein kinase inhibition, lethality of brine shrimp, and cytotoxicity against the human leukemia THP-1 cell line. The compounds demonstrated moderate to significant activities. Antioxidant activity of the synthesized compounds was evaluated by DPPH % inhibition with IC50 values. All compounds 1–6 showed notable antioxidant activity with DPPH having IC50 values between 23.2–15.1 and noteworthy brine shrimp lethality. Compound 6 demonstrated the highest cytotoxicity against brine shrimps with LC50 of 9.09 μg/mL. Protein kinase inhibition activity showed significant hyphea formation inhibition at 100 μg/disc with 10 to 13 mm clear zone of inhibition for the compounds 2–6. The compounds were screened for in vitro cytotoxicity using human leukemia cell line (THP-1 ATCC#TIB-202). Among all compounds, the most significant activity was demonstrated by compounds 6 and 5 with IC50 of 3.88 and 5.59 μg/mL which was comparable with the standard 5-flourouracil and vincristine drugs.