Displaying publications 1 - 20 of 105 in total

Abstract:
Sort:
  1. Taha M, Ismail NH, Jaafar FM, Khan KM, Yousuf S
    PMID: 23476582 DOI: 10.1107/S1600536813004388
    In the title benzoyl-hydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds, forming a chain along the b axis.
  2. Yousuf S, Khan KM, Salar U, Chigurupati S, Muhammad MT, Wadood A, et al.
    Eur J Med Chem, 2018 Nov 05;159:47-58.
    PMID: 30268823 DOI: 10.1016/j.ejmech.2018.09.052
    Acarbose and voglibose are well-known α-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential α-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 ± 0.16 μM to 2.38 ± 0.09 μM) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). A number of derivatives including 8-12 (IC50 = 1.68 ± 0.1 μM to 1.97 ± 0.07 μM) and 14-16 (IC50 = 1.61 ± 0.16 μM to 1.93 ± 0.07 μM) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α-amylase enzyme.
  3. Adegboye AA, Khan KM, Salar U, Aboaba SA, Kanwal, Chigurupati S, et al.
    Eur J Med Chem, 2018 Apr 25;150:248-260.
    PMID: 29533872 DOI: 10.1016/j.ejmech.2018.03.011
    Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC50 = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted.
  4. Taha M, Ismail NH, Zaki HM, Wadood A, Anouar EH, Imran S, et al.
    Bioorg Chem, 2017 12;75:235-241.
    PMID: 29031169 DOI: 10.1016/j.bioorg.2017.10.004
    3,4-Dimethoxybenzohydrazide derivatives (1-25) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2, 3, 4 and 5 with IC50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC50 value 21.40 ± 0.21 µM). Compounds 1, 6, 8, 18, 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.
  5. Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.
    Bioorg Chem, 2017 06;72:21-31.
    PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007
    On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
  6. Isaac IO, Al-Rashida M, Rahman SU, Alharthy RD, Asari A, Hameed A, et al.
    Bioorg Chem, 2019 02;82:6-16.
    PMID: 30267972 DOI: 10.1016/j.bioorg.2018.09.032
    Urease is a bacterial enzyme that is responsible for virulence of various pathogenic bacteria such as Staphylococcus aureus, Proteus mirabilis, Klebsiella pneumoniae, Ureaplasma urealyticum, Helicobacter pylori and Mycobacterium tuberculosis. Increased urease activity aids in survival and colonization of pathogenic bacteria causing several disorders especially gastric ulceration. Hence, urease inhibitors are used for treatment of such diseases. In search of new molecules with better urease inhibitory activity, herein we report a series of acridine derived (thio)semicarbazones (4a-4e, 6a-6l) that were found to be active against urease enzyme. Molecular docking studies were carried out to better comprehend the preferential mode of binding of these compounds against urease enzyme. Docking against urease from pathogenic bacterium S. pasteurii was also carried out with favorable results. In silico ADME evaluation was done to determine drug likeness of synthesized compounds.
  7. Ahmed U, Ong SK, Tan KO, Khan KM, Khan NA, Siddiqui R, et al.
    Int Microbiol, 2023 Nov 28.
    PMID: 38015290 DOI: 10.1007/s10123-023-00450-1
    Acanthamoeba are free living amoebae that are the causative agent of keratitis and granulomatous amoebic encephalitis. Alpha-Mangostin (AMS) is a significant xanthone; that demonstrates a wide range of biological activities. Here, the anti-amoebic activity of α-Mangostin and its silver nano conjugates (AMS-AgNPs) were evaluated against pathogenic A. castellanii trophozoites and cysts in vitro. Amoebicidal assays showed that both AMS and AMS-AgNPs inhibited the viability of A. castellanii dose-dependently, with an IC50 of 88.5 ± 2.04 and 20.2 ± 2.17 μM, respectively. Both formulations inhibited A. castellanii-mediated human keratinocyte cell cytopathogenicity. Functional assays showed that both samples caused apoptosis through the mitochondrial pathway and reduced mitochondrial membrane potential and ATP production, while increasing reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome-c reductase in the cytosol. Whole transcriptome sequencing of A. castellanii showed the expression of 826 genes, with 447 genes being up-regulated and 379 genes being down-regulated post treatment. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority of genes were linked to apoptosis, autophagy, RAP1, AGE-RAGE and oxytocin signalling pathways. Seven genes (PTEN, H3, ARIH1, SDR16C5, PFN, glnA GLUL, and SRX1) were identified as the most significant (Log2 (FC) value 4) for molecular mode of action in vitro. Future in vivo studies with AMS and nanoconjugates are needed to realize the clinical potential of this work.
  8. Khan KM, Jamil W, Ambreen N, Taha M, Perveen S, Morales GA
    Ultrason Sonochem, 2014 May;21(3):1200-5.
    PMID: 24398059 DOI: 10.1016/j.ultsonch.2013.12.011
    Aldazines (Bis-Schiff bases) 1-24 were synthesized using aromatic aldehydes (heterocyclic and benzaldehydes) and hydrazine hydrate under reflux using conventional heating and/or via ultrasound irradiation using BiCl3 as catalyst. Ultrasonication conditions with cat. BiCl3 proved to be an effective, environmentally friendly synthetic procedure. This methodology is robust in the presence of electron donating and electron withdrawing groups affording desired products with high yields (>95%) in just a couple of minutes vs. hours using conventional heating.
  9. Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.
    Acta Trop, 2023 Mar;239:106824.
    PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824
    Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
  10. Shahbaz MS, Anwar A, Saad SM, Kanwal, Anwar A, Khan KM, et al.
    Parasitol Res, 2020 Jul;119(7):2327-2335.
    PMID: 32476058 DOI: 10.1007/s00436-020-06710-7
    Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.
  11. Anwar A, Yi YP, Fatima I, Khan KM, Siddiqui R, Khan NA, et al.
    Parasitol Res, 2020 Jun;119(6):1943-1954.
    PMID: 32385711 DOI: 10.1007/s00436-020-06694-4
    Acanthamoeba causes diseases such as Acanthamoeba keratitis (AK) which leads to permanent blindness and granulomatous Acanthamoeba encephalitis (GAE) where there is formation of granulomas in the brain. Current treatments such as chlorhexidine, diamidines, and azoles either exhibit undesirable side effects or require immediate and prolonged treatment for the drug to be effective or prevent relapse. Previously, antifungal drugs amphotericin B, nystatin, and fluconazole-conjugated silver with nanoparticles have shown significantly increased activity against Acanthamoeba castellanii. In this study, two functionally diverse tetrazoles were synthesized, namely 5-(3-4-dimethoxyphenyl)-1H-tetrazole and 1-(3-methoxyphenyl)-5-phenoxy-1H-tetrazole, denoted by T1 and T2 respectively. These compounds were evaluated for anti-Acanthamoeba effects at different concentrations ranging from 5 to 50 μM. Furthermore, these compounds were conjugated with silver nanoparticles (AgNPs) to enhance their efficacy. Particle size analysis showed that T1-AgNPs and T2-AgNPs had an average size of 52 and 70 nm respectively. After the successful synthesis and characterization of tetrazoles and tetrazole-conjugated AgNPs, they were subjected to anti-Acanthamoeba studies. Amoebicidal assay showed that at concentration 10 μM and above, T2 showed promising antiamoebic activities between the two compounds while encystation and excystation assays reveal that both T1 and T2 have inhibited differentiation activity against Acanthamoeba castellanii. Conjugation of T1 and T2 to AgNP also increased efficacy of tetrazoles as anti-Acanthamoeba agents. This may be due to the increased bioavailability as AgNP allows better delivery of treatment compounds to A. castellanii. Human cell cytotoxicity assay revealed that tetrazoles and AgNPs are significantly less toxic towards human cells compared with chlorhexidine which is known to cause undesirable side effects. Cytopathogenicity assay also revealed that T2 conjugated with AgNPs significantly reduced cytopathogenicity of A. castellanii compared with T2 alone, suggesting that T2-conjugated AgNP is an effective and safe anti-Acanthamoeba agent. The use of a synthetic azole compound conjugated with AgNPs can be an alternative strategy for drug development against A. castellanii. However, mechanistic and in vivo studies are needed to explore further translational values.
  12. Mungroo MR, Shahbaz MS, Anwar A, Saad SM, Khan KM, Khan NA, et al.
    ACS Chem Neurosci, 2020 08 19;11(16):2438-2449.
    PMID: 31961126 DOI: 10.1021/acschemneuro.9b00596
    Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris. Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro. The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly (P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
  13. Zawawi NK, Rajput SA, Taha M, Ahmat N, Ismail NH, Abdullah N, et al.
    Bioorg Med Chem Lett, 2015 Oct 15;25(20):4672-6.
    PMID: 26330080 DOI: 10.1016/j.bmcl.2015.08.022
    Apoptotic cell death is the cause of the loss of insulin-producing β-cells in all forms of diabetes mellitus. The identification of small molecules capable of protecting cytokine-induced apoptosis could form the basis of useful therapeutic interventions. Here in, we present the discovery and synthesis of new benzimidazole derivatives, capable of rescuing pancreatic β-cells from cytokine-induced apoptosis. Three hydrazone derivatives of benzimidazole significantly increased the cellular ATP levels, reduced caspase-3 activity, reduced nitrite production and increased glucose-stimulated insulin secretion in the presence of proinflammatory cytokines. These findings suggest that these compounds may protect β-cells from the harmful effects of cytokines and may serve as candidates for therapeutic intervention for diabetes.
  14. Khan KM, Nadeem MF, Mannan A, Chohan TA, Islam M, Ansari SA, et al.
    Chem Biodivers, 2024 Jan;21(1):e202301375.
    PMID: 38031244 DOI: 10.1002/cbdv.202301375
    Trillium govanianum is a high-value medicinal herb, having multifunctional traditional and culinary uses. The present investigation was carried out to evaluate the phytochemical, biological and toxicological parameters of the T. govanianum Wall. ex D. Don (Family: Trilliaceae) roots collected from Azad Kashmir, Pakistan. Phytochemical profiling was achieved by determining total bioactive contents (total phenolic and flavonoid contents) and UHPLC-MS analysis. For biological evaluation, antioxidant activities (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation assays) and enzyme inhibition activities (against AChE, BChE, glucosidase, amylase, and tyrosinase) were performed. Moreover, cytotoxicity was assessed against three human carcinoma cell lines (MDA-MB-231, CaSki, and DU-145). The tested extract was found to contain higher total phenolics (7.56 mg GAE/g dry extract) as compared to flavonoid contents (0.45 mg RE/g dry extract). Likewise, for the antioxidant activity, higher CUPRAC activity was noted with 39.84 mg TE/g dry extract values. In the case of enzyme assays, higher activity was pointed out against the cholinesterase, glucosidase and tyrosinase enzymes. The plant extract displayed significant cytotoxicity against the cell lines examined. Moreover, the in-silico studies highlighted the interaction between the important phytochemicals and tested enzymes. To conclude, the assessed biological activity and the existence of bioactive phytochemicals in the studied plant extract may pave the way for the development of novel pharmaceuticals.
  15. Taha M, Imran S, Ismail NH, Selvaraj M, Rahim F, Chigurupati S, et al.
    Bioorg Chem, 2017 10;74:1-9.
    PMID: 28719801 DOI: 10.1016/j.bioorg.2017.07.001
    A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme.
  16. Seraj F, Kanwal, Khan KM, Khan A, Ali M, Khalil R, et al.
    Mol Divers, 2021 Feb;25(1):143-157.
    PMID: 31965436 DOI: 10.1007/s11030-019-10032-x
    Novel ibuprofen derivatives 1-19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2-19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1H-, and 13C-NMR spectroscopic techniques. The synthetic molecules 1-19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC50 = 2.96-178 μM as compared to the standard thiourea (IC50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2-4, 6, 7, 9, 11-15, 17, and 18 demonstrated remarkable inhibitory activity with IC50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC50 value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure-activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.
  17. Salar U, Khan KM, Taha M, Ismail NH, Ali B, Qurat-Ul-Ain, et al.
    Eur J Med Chem, 2017 Jan 05;125:1289-1299.
    PMID: 27886546 DOI: 10.1016/j.ejmech.2016.11.031
    Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1-26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, (1)H -NMR and (13)C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01-60.30 ± 1.40 μM as compared to the standard d-saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9-19, and 21-24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
  18. Taha M, Ullah H, Al Muqarrabun LMR, Khan MN, Rahim F, Ahmat N, et al.
    Bioorg Med Chem, 2018 01 01;26(1):152-160.
    PMID: 29183662 DOI: 10.1016/j.bmc.2017.11.028
    Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.
  19. Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.
    Bioorg Chem, 2017 06;72:89-101.
    PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014
    Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
  20. Salar U, Khan KM, Jabeen A, Faheem A, Fakhri MI, Saad SM, et al.
    Bioorg Chem, 2016 12;69:37-47.
    PMID: 27669119 DOI: 10.1016/j.bioorg.2016.09.006
    Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2±9.2μM). Eleven compounds 6 (IC50=46.60±14.6μM), 8 (IC50=11.50±6.5μM), 15 (IC50=21.40±12.2μM), 19 (IC50=5.75±0.86μM), 22 (IC50=10.27±1.06μM), 23 (IC50=33.09±5.61μM), 24 (IC50=4.93±0.58μM), 25 (IC50=21.96±14.74μM), 29 (IC50=12.47±9.2μM), 35 (IC50=20.20±13.4μM) and 37 (IC50=14.47±5.02μM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4-43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links