Farooq U

References (7)

Title : Evaluation of pyrimidine\/pyrrolidine-sertraline based hybrids as multitarget anti-Alzheimer agents: In-vitro, in-vivo, and computational studies - Javed_2023_Biomed.Pharmacother_159_114239
Author(s) : Javed MA , Jan MS , Shbeer AM , Al-Ghorbani M , Rauf A , Wilairatana P , Mannan A , Sadiq A , Farooq U , Rashid U
Ref : Biomed Pharmacother , 159 :114239 , 2023
Abstract : Alzheimer's disease (AD) is a complex, multifactorial and most prevalent progressive neurodegenerative ailment. Its multifactorial and complex nature causes the lack of disease modifying drugs. Hence, multi-target drug design strategies have been adopted to halt the progression of AD. In current research, we applied multitarget strategy to tackle multifactorial nature of AD. Rational design and synthesis of framework of hybrids containing Pyrimidine/pyrrolidine-sertraline scaffolds were carried out. The synthesized compounds were further evaluated for their in-vitro enzyme inhibition potential against cholinesterases, monoamine oxidases and beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Compound 19 emerged as an optimal multipotent hybrid with IC(50) values of 0.07smicroM, 0.09smicroM, 0.63smicroM, 0.21smicroM and 0.73smicroM against AChE, BChE, MAO-A, MAO-B and BACE-1 respectively. After in-vivo cytotoxicity and in-vitro PAMPA blood brain barrier permeation assays, a number of widely used behavioral assessment tests were also performed for the evaluation of memory and learning.Determination of biochemical parameters showed low levels of acetylcholinesterase by the treatment with synthesized compounds. Furthermore, levels of neurotransmitters such as serotonin, dopamine and noradrenaline were also analyzed. Increased neurotransmitter levels showed the improved short and long-term memory as well as enhanced learning behavior. Docking studies on the target enzymes showed correlation with the experimental in-vitro enzyme inhibition results.
ESTHER : Javed_2023_Biomed.Pharmacother_159_114239
PubMedSearch : Javed_2023_Biomed.Pharmacother_159_114239
PubMedID: 36638595

Title : Diclofenac derivatives as concomitant inhibitors of cholinesterase, monoamine oxidase, cyclooxygenase-2 and 5-lipoxygenase for the treatment of Alzheimer's disease: synthesis, pharmacology, toxicity and docking studies - Javed_2022_RSC.Adv_12_22503
Author(s) : Javed MA , Bibi S , Jan MS , Ikram M , Zaidi A , Farooq U , Sadiq A , Rashid U
Ref : RSC Adv , 12 :22503 , 2022
Abstract : Targeting concomitantly cholinesterase (ChEs) and monoamine oxidases (MAO-A and MAO-B) is a key strategy to treat multifactorial Alzheimer's disease (AD). Moreover, it is reported that the expression of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is increased significantly in the brain of AD patients. Using the triazole of diclofenac 12 as a lead compound, we synthesized a variety of analogs as multipotent inhibitors concomitantly targeting COX-2, 5-LOX, AChE, BChE, MAO-A and MAO-B. A number of compounds showed excellent in vitro inhibition of the target biological macromolecules in nanomolar concentration. Compound 39 emerged as the most potent multitarget ligand with IC(50) values of 0.03 microM, 0.91 microM, 0.61 microM, 0.01 microM 0.60 microM and 0.98 microM towards AChE, BChE, MAO-A, MAO-B, COX-2 and 5-LOX respectively. All the biologically active compounds were found to be non-neurotoxic and blood-brain barrier penetrant by using PAMPA assay. In a reversibility assay, all the studied active compounds showed reversibility and thus were found to be devoid of side effects. MTT assay results on neuroblastoma SH-SY5Y cells showed that the tested compounds were non-neurotoxic. An in vivo acute toxicity study showed the safety of the synthesized compounds up to a 2000 mg kg(-1) dose. In docking studies three-dimensional construction and interaction with key residues of all the studied biological macromolecules helped us to explain the experimental results.
ESTHER : Javed_2022_RSC.Adv_12_22503
PubMedSearch : Javed_2022_RSC.Adv_12_22503
PubMedID: 36105972

Title : Macrocyclic sulfone derivatives: Synthesis, characterization, in vitro biological evaluation and molecular docking - Ibrahim_2021_Drug.Dev.Res_82_562
Author(s) : Ibrahim M , Latif A , Ammara , Ali A , Ribeiro AI , Farooq U , Ullah F , Khan A , Al-Harrasi A , Ahmad M , Ali M
Ref : Drug Dev Res , 82 :562 , 2021
Abstract : An artificial series of macrocycles based on 4,4'-sulfonyldiphenol intermediate was synthesized using a multistep procedure involving oxidation of bisphenol sulfide, etherification of phenolic hydroxyl groups, and final ring closure with different diamines. Different chemical species having aromatic, heteroaromatic, and aliphatic characters were incorporated into macrocyclic frameworks in the final step of ring closure. This simple and easily executable synthetic strategy was applied to synthesize 15 macrocycles (5a-o) in excellent yields. Characterization of the synthesized products was achieved through well-known modern spectroscopic techniques such as IR, NMR, and Mass. Macrocycles 5m and 5n were found to show significant AChE inhibition with IC(50) values of 76.9+/-0.24 and 71.2+/-0.77microM, respectively. Macrocycle 5n was also found to be an active inhibitor of butyrylcholinesterase (BChE) with IC(50) score of 55.3+/-0.54microM. Among others, macrocycle 5l cyclized with o-phenylenediamine demonstrated moderate inhibition with IC(50) value of 81.1+/-0.54microM. Increasing interest in studying interactions of macrocycles with different enzymatic targets compelled us to design and synthesize sulfone-based macrocycles that might prove as highly potent class of biologically active compounds.
ESTHER : Ibrahim_2021_Drug.Dev.Res_82_562
PubMedSearch : Ibrahim_2021_Drug.Dev.Res_82_562
PubMedID: 33368483

Title : Combined in Vitro and in Silico Studies for the Anticholinesterase Activity and Pharmacokinetics of Coumarinyl Thiazoles and Oxadiazoles - Ibrar_2018_Front.Chem_6_61
Author(s) : Ibrar A , Khan A , Ali M , Sarwar R , Mehsud S , Farooq U , Halimi SMA , Khan I , Al-Harrasi A
Ref : Front Chem , 6 :61 , 2018
Abstract : In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a-o) and coumarin-oxadiazole 11(a-h) hybrids have been designed and synthesized. All the compounds were characterized by (1)H- and (13)C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 +/- 0.09 muM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 +/- 3.37 muM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 +/- 0.23 muM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 +/- 0.09 muM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of -10.19, -9.97, -9.68, and -11.03 Kcal.mol(-1), respectively. The major interactions include hydrogen bonding, pi-pi stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of -9.9, -7.4, and -8.2 Kcal.mol(-1), respectively, with the active site of BuChE building pi-pi stacking with Trp82 and water bridged interaction.
ESTHER : Ibrar_2018_Front.Chem_6_61
PubMedSearch : Ibrar_2018_Front.Chem_6_61
PubMedID: 29632858

Title : Neurologically Potent Molecules from Crataegus oxyacantha\; Isolation, Anticholinesterase Inhibition, and Molecular Docking - Ali_2017_Front.Pharmacol_8_327
Author(s) : Ali M , Muhammad S , Shah MR , Khan A , Rashid U , Farooq U , Ullah F , Sadiq A , Ayaz M , Ahmad M , Latif A
Ref : Front Pharmacol , 8 :327 , 2017
Abstract : Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source. Important natural products like beta-Sitosterol-3-O-beta-D-Glucopyranoside (3), lupeol (4), beta-sitosterol (5), betulin (6), betulinic acid (7), oleanolic acid (8), and chrysin (9) have also been isolated from C. oxyacantha. Overall, all the compounds exhibited an overwhelming acetylcholinesterase (AChE) inhibition potential in the range 5.22-44.47 muM. The compound 3 was prominent AChE inhibitor with IC50 value of 5.22 muM. Likewise, all the compounds were also potent in butyrylcholinesterase (BChE) inhibitions with IC50s of up to 0.55-15.36 muM. All the compounds, except 3, were selective toward BChE. Mechanism of the inhibition of both the enzymes were further studied by docking procedures using Genetic Optimization for Ligand Docking suit v5.4.1. Furthermore, computational blood brain barrier prediction of the isolated compounds suggest that these are BBB+.
ESTHER : Ali_2017_Front.Pharmacol_8_327
PubMedSearch : Ali_2017_Front.Pharmacol_8_327
PubMedID: 28638340

Title : Isolation of four new pterocarpans from Zygophyllum eurypterum (Syn. Z. atriplicoides) with enzyme-inhibition properties - Ahmad_2006_Chem.Biodivers_3_996
Author(s) : Ahmad VU , Iqbal S , Nawaz SA , Choudhary MI , Farooq U , Ali ST , Ahmad A , Bader S , Kousar F , Arshad S , Tareen RB
Ref : Chem Biodivers , 3 :996 , 2006
Abstract : Four new pterocarpans, atricarpan A (=(-)-1,2-dihydroxy-4-(hydroxymethyl)-3,9-dimethoxypterocarpan; 1), atricarpan B (=(-)-2,3-ethylenedioxy)-1,4-dihydroxy-9-methoxypterocarpan; 2), atricarpan C (=(-)-1,9-dimethoxypterocarpan-3-carboxylic acid; 3), and atricarpan D (=(-)-2,9-dimethoxy-4-(5-oxohexyl)pterocarpan; 4) were isolated from the BuOH extract of the whole plant of Zygophyllum eurypterum. The structure elucidations of those compounds were based primarily on 1D- and 2D-NMR analysis, including COSY, HMBC, and HMQC correlations. Compounds 1-4 also inhibited butyrylcholinesterase (BChE; EC enzyme in a concentration-dependent manner with IC(50) values between 12.5-65.0 microM. Similarly, compounds 1 and 4 inhibited lipoxygenase (LOX; EC and acetylcholinesterase (AChE; EC enzymes with IC50 values of 13.5 and 20.5 muM, respectively.
ESTHER : Ahmad_2006_Chem.Biodivers_3_996
PubMedSearch : Ahmad_2006_Chem.Biodivers_3_996
PubMedID: 17193332

Title : Three new cholinesterase-inhibiting cis-clerodane diterpenoids from Otostegia limbata - Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
Author(s) : Ahmad VU , Khan A , Farooq U , Kousar F , Khan SS , Nawaz SA , Abbasi MA , Choudhary MI
Ref : Chem Pharm Bull (Tokyo) , 53 :378 , 2005
Abstract : Three new tricyclic cis-clerodane type diterpenoids trivially named as limbatolide A (1), limbatolide B (2) and limbatolide C (3) have been isolated from the roots of Otostegia limbata along with two known compounds; oleanic acid and beta-sitosterol. The structure elucidation of the new compounds was based primarily on two-dimensional (2D) NMR techniques. Compounds 1-3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC and butyrylcholinesterase (BChE; EC enzymes, respectively.
ESTHER : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedSearch : Ahmad_2005_Chem.Pharm.Bull.(Tokyo)_53_378
PubMedID: 15802835