Analytical Chemistry, Pharmacology, Toxicology and Pharmaceutics
64
Scopus Publications
1595
Scholar Citations
20
Scholar h-index
40
Scholar i10-index
Scopus Publications
Unique Bidentate Chelators of Functionalized Heterocyclic Fluoroquinolones with Dual Anti-Inflammatory and Selective Cytotoxic Effects via a C7-C8 Ethylene Diamine Bridge Moneera Alzghoul, Yusuf Al-Hiari, Violet Kasabri, Imad Hamdan, Shereen Arabiyat, et al. Current Medicinal Chemistry, 2026 Introduction: In the context of repurposing antimicrobial fluoroquinolones (FQs), we propose that their increased efficacy is attributable to the lipophilic properties of the newly developed FQs. Methods: This study involved the synthesis of 21 lipophilic-acid chelating fluoroquinolones (FQs) and their subsequent screening approaches for selective antiproliferative, antioxidant, and anti-inflammatory activities Results: Notably, the reduced FQ series, specifically 14c, demonstrated radical scavenging activities for NO and DPPH that were comparable to the referencing agents. In contrast to the others, the reduced 10a, 10b, and 14b FQs exhibited significant antioxidant effects. Predominantly, MCF7, HT29, T47D, and SW480 were the best target cell lines for the new FQs to exhibit their antiproliferative activities. In fact, many FQ derivatives have revealed IC50 values below 10 µM, mainly with MCF7 and HT29cell lines. Among the three synthesized series (nitro, reduced, and triazolo), the compounds (10a-d and 14a-d) of the reduced series exhibited the highest activities (lowest IC50) against the strongest four cell lines. All reduced series of hexyl phenyl 14a, 14c, and 14d with para-halogens were stronger than their hexyl amine counterparts 10a, 10c, and 10d. The selectivity indices for the new FQs were either equipotent or more potent than the reference cisplatin. Discussion: The remarkable effects of the reduced series 14a, 14b, 14c, 10a, 10c, and 10d stemmed from metal chelation within the C8-C7 ethylene diamine bridge. Furthermore, the spatial and steric constraints introduced by the N1 substituent ultimately influenced the chelation geometry. Complexation studies revealed that central iron chelation is the predominant intracellular mechanism, whereas zinc chelation is the primary mode of interaction with the zinc-dependent metalloenzyme Glo-I. Mechanistically, nitroFQs 9d, 13a, and 13d and their respective reduced FQs 14a and 14d were shown to exhibit unprecedentedly equipotent Glo-I enzymatic inhibition, matching the IC50 value of myricetin (3.5 µM). Appreciably significant GLo-I inhibition with IC50 values ranging from 24-52 µM was obtained for nitroFQs and their reduced FQs in the ascending order of 9c < 9b < 13b < 14b < 10b < 10c < 10d. Conclusion: The mechanism of action of the FQs involved acidic functional groups and a C7-C8 ethylenediamine chelation bridge, with iron chelation being the predominant pathway
Deferasirox and Ciprofloxacin: Potential Ternary Complex Formation With Ferric Iron, Pharmacodynamic, and Pharmacokinetic Interactions Imad I. Hamdan, Ruba T. Tarawneh, Firas Awwadi, Duaa Al-Qattan, Ahmad I. Hamdan, et al. Scientific World Journal, 2024 The main aim of this work was to assess the potential formation of ternary chelate complexes, involving deferasirox (DFX), ciprofloxacin (CP), and ferric iron. The coadministration of CP along with DFX might modulate its efficacy, so it is important that it be investigated. A ternary complex involving DFX, CP, and iron (DFX‐CP‐Fe) was prepared and characterized. Theoretical chemistry calculations were performed to measure the equilibrium constants of complexes. Two groups of rats were exposed to DFX or DFX with CP. The level of DFX in plasma was measured, and histological assessments of relevant organs were made. Levels of iron in selected tissues were measured. The formation of ternary complexes was confirmed. Two ternary complexes are thermodynamically favored. The first one of ratio (DFX:CP:Fe) was shown to be favorable with an equilibrium constant of 2 × 107. The second one with ratio (DFX:CP:2Fe) is more thermodynamically favored with an equilibrium constant of 2.0 × 1060. Rats treated with a combination of DFX and CP exhibited lower levels of iron in dried red blood cells in comparison to those treated with DFX alone (p value = 0.012). They also exhibited lower levels of DFX in plasma. Histological assessments of the relevant tissues showed a clear difference in the level of deposited iron in the spleen. In conclusion, ternary complexes are formed, and some with exceptionally high constants. The obtained data indicate a potentially favorable role of CP because while it resulted in a decrease in the level of DFX, it pharmacodynamically produced more effect.
Metal Chelators as Anticancer Approach: Part I; Novel 7-Anisidine Derivatives with Multidentate at 7-8 Carbons of Fluoroquinolone Scaffold as Potential Chelator Anticancer and Antilipolytic Candidates Yusuf Al-Hiari, Shereen Arabiyat, Violet Kasabri, Imad Hamdan, Ihab Almasri, et al. Jordan Journal of Pharmaceutical Sciences, 2023 Background: Cancer is one of the greatest troubling maladies currently. It is believed that it is the second reason for death following cardiovascular maladies. Owing to the multiplicity of its types, stages and genetic basis, there is no existing drug to cure all types of cancer. Resistance to present drugs and severe adverse effects are other challenges in the struggle against cancer. In such pursuit, fluoroquinolones (FQs) have the potential as antiproliferative compounds due to safety, low cost, and absence of resistance.
 Aims: In this study, we aim to synthesize biologically active compounds that have dual anticancer and anti-lipase potential. Sixteen compounds were prepared, fully characterized, and studied through identification of IC50 values against the highly susceptible cancer cell lines.
 Methods: In this work we are concerned with synthesizing biologically active compounds that belong to fluoroquinolones (FQs) with dual anti-colorectal cancer and anti-lipase activity, owing to association between cancer and obesity, conduct titration and docking experiments to validate our hypothesis.
 Results: In vitro findings indicated that these compounds demonstrated promising anticancer activity against tested cell lines in micromolar range with a potency comparable to cisplatin. Compound 11 exhibited approximately doubled potency compared to cisplatin against SW620 colorectal cancer cell line with IC50 3.2 μM which proposes FQs as potent antiproliferative agents. The synthesized Fluoroquinolone (FQ) compounds were further screened for their in vitro anti-lipase potential. The findings demonstrated that all the screened compounds have demonstrated remarkable anti-lipase activity, as compared to control molecule orlistat. Compound 9 exhibited comparable activity to orlistat against pancreatic lipase with IC50 0.4 μM which proposes FQs as potent pancreatic lipase inhibitors.
 Conclusions: The anticancer potential of these derivatives is referred to their ability to inhibit Topo II which indicates that chelation is the mechanism of inhibition of Topo II emphasized with titration and docking experiments.
IR microspectroscopic investigation of the interaction of some losartan salts with human stratum corneum protein and its effect on losartan transdermal permeation Randa S. H. Mansour, Aamal Y. Al Khawaja, Imad I. Hamdan, Enam A. Khalil Plos One, 2023 The interaction of pharmacologically active drugs with SC biochemical components is underestimated in pharmaceutical research. The aim of this research was to illustrate that some drugs intended for transdermal delivery could interact with the protein component of SC. Such interactions could be in favor of or opposition to their percutaneous absorption. IR microspectroscopy was used to delineate possible interaction of SC keratin with three losartan salts LOS-K, LOS-DEA and LOS-AML salts in addition to AML-BES salt. The results of PCA, combined with comparisons of average second derivative spectra of SC samples treated with these salts and the control SC, showed that LOS-DEA did not interact with SC, thus providing base line permeation of losartan. AML-BES, LOS-AML and LOS-K salts modified the conformational structure of keratin. The disorganization effect on the α-helical structure and induced formation of parallel β-sheets and random coils were in the order of AML-BES˃LOS-AML˃LOS-K. The order of the impact of treatments which resulted in increased formation of β-turns was AML-BES˃LOS-AML. The formation of antiparallel β-sheets was manifested by LOS-AML. Thus, the overall effect of these salts on the SC protein was AML-BES˃LOS-AML˃LOS-K. The impact of LOS-K was associated with improved permeation whereas the impact of LOS-AML was associated with hindered permeation of both losartan and amlodipine. There is a possibility that losartan and amlodipine when present in combination inside SC, their binding to the protein is enhanced leading to being retained within SC.
Preparation, Characterization and Transdermal Permeation of Losartan-Amlodipine Molecular Salt Aamal Y. Al Khawaja, Enam A. Khalil, Randa SH. Mansour, Imad I. Hamdan Jordan Journal of Pharmaceutical Sciences, 2022 Drug molecular salt composed of the antihypertensive compound losartan (LOS) as the anion and the antihypertensive drug amlodipine (AMLO) was prepared. The prepared salt (LOS-AMLO) was characterized by measurement of purity, water content, solubility, partition coefficient, and melting behavior in addition to common spectroscopic techniques (UV, FTIR and NMR). NMR spectral shifts of particular protons of LOS in particular were quite useful in explaining the points of interaction and association between the two ionic species so that a 3D structure could be proposed. LOS-AMLO exhibited a significantly lower melting point than its parent compounds (65 oC) which places the salt within the ionic liquids category, in a broad sense of the definition. LOS-AMLO was found to have much lower solubility than LOS with a substantially higher apparent partition coefficient. The high partition coefficient together with lower melting temperature is favorable properties for the transdermal permeation of pharmaceuticals. However, diffusion studies through the human stratum corneum, from an aqueous solution based on propylene glycol revealed a vast decrease in the permeation of both drugs from the molecular (ionic liquid) salt form. Interestingly the experiment demonstrated that the salt structure might be maintained during permeation but with indications of strong chemical interaction between the salt and the constituents of the barrier.
Trimolecular Co-crystals of Ciprofloxacin, p-Coumaric Acid, and Benzoic Acid or Salicylic Acid Firas F. Awwadi, Lina A. Dahabiyeh, Imad I. Hamdan Journal of Chemical Crystallography, 2022 Molecular salts formation is a simple and widely used approach to alter the physicochemical properties of active pharmaceutical ingredients, such as ciprofloxacin (CP), without modifying their chemical structures. In the current work, two co-crystals of p-coumaric acid (PCMA) and organic salts of CP cation (CPH) were prepared and characterized in solid state by X-ray diffraction and by NMR spectroscopy in solution. The two organic salts are CPH:benzoate anion (CPH:BA) and CPH:salicylate anion (CPH:SA). To our knowledge, these are the first two examples of co-crystals of CPH organic salt and a different organic acid. In the two co-crystals (CPH:BA:PCMA and CPH:SA:PCMA), the anion (BA or SA) connects the PCMA molecules and the CPH via O–H∙∙∙O and N–H∙∙∙O hydrogen bonding interactions. The ratio between the three crystalline species in the two co-crystals (CPH:BA:PCMA and CPH:SA:PCMA) is (1:1:1), the ratio was confirmed in solution by NMR spectroscopy. Co-Crystals of ciprofloxacinuim cation salts of salicylate or benzoate anions and p-coumaric acid have been studied in solution using NMR spectroscopy and in solid state using X-ray crystallography
Development and Validation of a Stability-indicating HPLC Method for Determination of Insulin Detemir and Preservatives in their Injection Products Dua'a G. H. Faraha, E. Khalil, Randa Mansourc, I. Hamdan Analytical and Bioanalytical Chemistry Research, 2022 Insulin detemir (ID) is a long-acting form of insulin that is characterized by the covalent attachment of a lipophilic tail of myristate, and commercially available as Levemir®. No satisfactory simple isocratic stability-indicating HPLC method has been reported for its quality control. A novel simple and isocratic reversed-phase HPLC method was developed and validated for the simultaneous determination of ID along with its dosage form additives in the available commercial preparations. The method employed C4 column (5μm, 250 × 4.6 mm), a mobile phase consisting of 50 mM phosphate buffer pH 2.7, acetonitrile, triethylamine (62:37:1) and 0.02 g/ml sodium sulfate, that was delivered isocraticaly at a flow rate of 1.5 ml/min, and detection performed at 214nm. The method was properly validated and was shown linear over the range 80–120% of the assay concentration for ID, phenol, and m-cresol. The method was also selective, specific, precise, and accurate. Furthermore, the validated method was applied to separate the major degradation products in those preparations. Forced degradation studies in different pH values, which are the first to be reported for ID, showed that the degradation products were baseline separated from ID itself and/or other formulation additives. Thus, the method has been demonstrated to be a stability-indicating assay.
Preparation and physicochemical characterization of atorvastatin choline salt and its potential for transdermal permeation Jordan Journal of Pharmaceutical Sciences, 2020
Unique Bidentate Chelators of Functionalized Heterocyclic Fluoroquinolones with Dual Anti-Inflammatory and Selective Cytotoxic Effects via a C7-C8 Ethylene Diamine Bridge. M Alzghoul, Y Al-Hiari, V Kasabri, I Hamdan, S Arabiyat, Q Al-Balas, ... Current Medicinal Chemistry , 2026 2026 Citations: 4
Valsartan–Choline: Preparation, Characterization, and transdermal permeation II Hamdan, D El-Sabawi, RR Ramazanov, AO Lantushenko, ... Journal of Molecular Liquids 419, 126827 , 2025 2025 Citations: 1
Deferasirox and Ciprofloxacin: Potential Ternary Complex Formation With Ferric Iron, Pharmacodynamic, and Pharmacokinetic Interactions II Hamdan, RT Tarawneh, F Awwadi, D Al-Qattan, AI Hamdan, F Afifi The Scientific World Journal 2024 (1), 9309491 , 2024 2024
Metal chelators as anticancer approach: Part I; novel 7-anisidine derivatives with multidentate at 7-8 carbons of fluoroquinolone scaffold as potential chelator anticancer and … Y Al-Hiari, S Arabiyat, V Kasabri, I Hamdan, I Almasri, MY Mohammad, ... Jordan Journal of Pharmaceutical Sciences 16 (2), 402-425 , 2023 2023 Citations: 4
IR microspectroscopic investigation of the interaction of some losartan salts with human stratum corneum protein and its effect on losartan transdermal permeation RSH Mansour, AY Al Khawaja, II Hamdan, EA Khalil Plos one 18 (6), e0287267 , 2023 2023 Citations: 1
https://www.researchgate.net/publication … R Mansour, AYA Khawaja, I Hamdan, EA Khalil Plos One 18 (6), e0287267 , 2023 2023
Curcumin-betaine solid dispersion for enhancing curcumin dissolution and potentiating pharmacological synergism in gastric cancer cells G Kamal, S Abdullah, F Basingab, A Bani-Jaber, II Hamdan Journal of Drug Delivery Science and Technology 79, 103951 , 2023 2023 Citations: 12
Preparation, Characterization and Transdermal Permeation of Losartan-Amlodipine Molecular Salt. AY Al Khawaja, EA Khalil, RSH Mansour, II Hamdan Jordan Journal of Pharmaceutical Sciences 15 (4) , 2022 2022 Citations: 5
Interaction of esomeprazole with insulin detemir and human albumin: a potential cause of hypoglycemia II Hamdan, DGH Farah, EA Khalil, RSH Mansour, H Abdel-Halim. Biophysical Chemistry 285, 106809 , 2022 2022 Citations: 4
Development and Validation of a Stability-indicating HPLC Method for Determination of Insulin Detemir and Preservatives in their Injection Products DGH Faraha, EA Khalil, RSH Mansourc, II Hamdan Analytical and Bioanalytical Chemistry Research 9 (1), 85-99 , 2022 2022 Citations: 1
HPLC method development/validation and skin diffusion study of caffeine, methyl paraben and butyl paraben as skin–diffusing model drugs ALSAS Randa S. H. MansourID1 *, Imad I. Hamdan2 , Mutaz S. H. Salem1 , Enam ... Plos One 16 (3) , 2021 2021 Citations: 11
Characterization of insulin mucoadhesive buccal films: spectroscopic analysis and in vivo evaluation M Diab, AS Sallam, I Hamdan, R Mansour, R Hussain, G Siligardi, ... Symmetry 13 (1), 88 , 2021 2021 Citations: 14
Preparation, characterization and antimicrobial assessment of selected ciprofloxacin salts IH IMAD, ELS DINA, D RULA, AD LINA Acta Pharmaceutica | 71, 365-382 , 2020 2020 Citations: 6
Studies on potential interaction between cinacalcet hydrochloride and diclofenac sodium II Hamdan, D El-Sabawi, NM Tverdokhleb, AO Lantushenko, ... Biophysical Chemistry 266, 106460 , 2020 2020 Citations: 2
Chromatographic behaviour and analytical method development for metformin HCl: application to permeation studies through Caco-2 cells II Hamdan, DG Farah, RAD Abu-Dahab Acta Poloniae Pharmaceutica-Drug Research 77 (1), 11-21 , 2020 2020 Citations: 2
Preparation and physicochemical characterization of atorvastatin choline salt and its potential for transdermal permeation R Tarawneh 2020 Citations: 3
Interaction of pseudoephedrine and azithromycin with losartan: Spectroscopic, dissolution and permeation studies NS Al-Dmour, RMN Abu-Dahab, MP Evstigneev, VV Kostjukov, ... Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 221, 117194 , 2019 2019 Citations: 4
Pancreatic lipase inhibitory activity of selected pharmaceutical agents II Hamdan, VN Kasabri, YM Al-Hiari, D El-Sabawi, H Zalloum Acta Pharmaceutica 69 (1), 1-16 , 2019 2019 Citations: 13
Studies on the interaction between ciprofloxacin hydrochloride and diclofenac sodium. D El-Sabawi, R Abu-Dahab, AG Al Bakri, II Hamdan Tropical Journal of Pharmaceutical Research 18 (2) , 2019 2019 Citations: 7
The effect of ferrous ions, calcium ions and citric acid on absorption of ciprofloxacin across caco-2 cells: practical and structural approach D El-Sabawi, R Abu-Dahab, WA Zalloum, F Ijbara, II Hamdan Drug Development and Industrial Pharmacy 45 (2), 292-303 , 2019 2019 Citations: 19
MOST CITED SCHOLAR PUBLICATIONS
Studies on the in vitro and in vivo hypoglycemic activities of some medicinal plants used in treatment of diabetes in Jordanian traditional medicine II Hamdan, FU Afifi Journal of ethnopharmacology 93 (1), 117-121 , 2004 2004 Citations: 306
In vitro and in vivo acute antihyperglycemic effects of five selected indigenous plants from Jordan used in traditional medicine V Kasabri, FU Afifi, I Hamdan Journal of ethnopharmacology 133 (2), 888-896 , 2011 2011 Citations: 147
Spectroscopic and HPLC methods for the determination of alendronate in tablets and urine SK Al Deeb, II Hamdan, SM Al Najjar Talanta 64 (3), 695-702 , 2004 2004 Citations: 106
Development and validation of a stability indicating capillary electrophoresis method for the determination of metformin hydrochloride in tablets II Hamdan, AKB Jaber, AM Abushoffa Journal of pharmaceutical and biomedical analysis 53 (5), 1254-1257 , 2010 2010 Citations: 82
Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers N Hakooz, I Hamdan Current Drug Metabolism 8 (1), 9-15 , 2007 2007 Citations: 77
Solubility enhancement of glibenclamide in choline–tryptophan ionic liquid: Preparation, characterization and mechanism of solubilization MA Alawi, II Hamdan, ALSA Sallam, NA Heshmeh Journal of Molecular Liquids 212, 629-634 , 2015 2015 Citations: 59
Evaluation of the acute antihyperglycemic effects of four selected indigenous plants from Jordan used in traditional medicine V Kasabri, FU Afifi, I Hamdan Pharmaceutical biology 49 (7), 687-695 , 2011 2011 Citations: 52
Use of capillary electrophoresis in the study of ligand-DNA interactions II Hamdan, GG Skellern, RD Waigh Nucleic acids research 26 (12), 3053-3058 , 1998 1998 Citations: 49
Predictors of nonadherence in children and adolescents with epilepsy: A multimethod assessment approach M Alsous, I Hamdan, M Saleh, J McElnay, R Horne, A Masri Epilepsy & Behavior 85, 205-211 , 2018 2018 Citations: 37
Screening of Jordanian flora for α-amylase inhibitory activity II Hamdan, FU Afifi Pharmaceutical Biology 46 (10-11), 746-750 , 2008 2008 Citations: 32
Elucidation of penetration enhancement mechanism of Emu oil using FTIR microspectroscopy at EMIRA laboratory of SESAME synchrotron RSH Mansour, AA Sallam, II Hamdan, EA Khalil, I Yousef Spectrochimica acta part A: molecular and biomolecular spectroscopy 185, 1-10 , 2017 2017 Citations: 31
Sodium mefenamate as a solution for the formulation and dissolution problems of mefenamic acid A Bani-Jaber, I Hamdan, B Al-Khalidi Chemical and Pharmaceutical Bulletin 55 (8), 1136-1140 , 2007 2007 Citations: 30
In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions A Bani-Jaber, I Alshawabkeh, S Abdullah, I Hamdan, A Ardakani, ... AAPS PharmSciTech 18 (5), 1750-1759 , 2017 2017 Citations: 26
In vitro alpha amylase inhibitory effect of some clinically-used drugs II Hamdan, F Afifi, MO Taha Die Pharmazie-An International Journal of Pharmaceutical Sciences 59 (10 … , 2004 2004 Citations: 26
Development of a capillary electrophoresis method for the determination of orphenadrine citrate in tablets in the presence of paracetamol DN Haj-Ali, II Hamdan Saudi Pharmaceutical Journal 18 (4), 233-237 , 2010 2010 Citations: 25
Superconducting and normal state behaviors of (Tl, Bi) Sr2− xTixCa0. 9Y0. 1Cu2O7 ceramics AK Yahya, WF Abdullah, MH Jumali, H Imad, R Abd-Shukor Ceramics international 30 (7), 1591-1595 , 2004 2004 Citations: 25
Comparative in vitro investigations of the interaction between some macrolides and Cu (II), Zn (II) and Fe (II) II Hamdan Die Pharmazie-An International Journal of Pharmaceutical Sciences 58 (3 … , 2003 2003 Citations: 25
Pharmaceutical evaluation of metformin HCl products available in the Jordanian market II Hamdan, AKB Jaber Jordan J Pharm Sci 3 (22), 1-7 , 2010 2010 Citations: 23
Changes in doping state of (Tl, Pb) Sr1212 superconductors with Yb substitution at Sr site AK Yahya, WF Abdullah, H Imad, MH Jumali Physica C: Superconductivity and its applications 463, 474-477 , 2007 2007 Citations: 22
Capillary electrophoresis in the analysis of pharmaceuticals in environmental water: A critical review II Hamdan Journal of Liquid Chromatography & Related Technologies 40 (3), 111-125 , 2017 2017 Citations: 21
Publications
Interaction of esomeprazole with insulin detemir and human albumin: a potential cause of hypoglycemia
Imad I. Hamdana*, Dua'a GH. Farahb, Enam A. Khalilc, Randa SH. Mansourd, Heba Abdel-Halime.
Biophysical Chemistry, 285, 106809
IR microspectroscopic investigation of the interaction of some losartan salts with human stratum corneum protein and its effect on losartan transdermal permeation. Randa S H Mansour , Aamal Y Al Khawaja , Imad I Hamdan , Enam A Khalil. PLoS One. 2023 Jun 15;18(6):e0287267. doi: 10.1371/.
