Latif A

References (10)

Title : Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors - Ibrahim_2024_Bioorg.Chem_144_107144
Author(s) : Ibrahim M , Halim SA , Latif A , Ahmad M , Ali S , Ullah S , Khalid A , Abdalla AN , Khan A , Al-Harrasi A , Ali M
Ref : Bioorg Chem , 144 :107144 , 2024
Abstract : A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques ((1)H NMR, (13)C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC(50) = 26.3 +/- 0.4 microM) and 11 (IC(50) = 28.4 +/- 0.5 microM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC(50) values ranging from 35.2 +/- 1.1 microM to 64.4 +/- 0.3 microM. On the other hand, 5 (IC(50) = 22.0 +/- 1.1 microM) and 27 (IC(50) = 31.3 +/- 1.3 microM) displayed significant, and 19 (IC(50) = 92.6 +/- 0.4 microM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.
ESTHER : Ibrahim_2024_Bioorg.Chem_144_107144
PubMedSearch : Ibrahim_2024_Bioorg.Chem_144_107144
PubMedID: 38281382

Title : New supramolecules of bis(acylhydrazones)-linked bisphenol sulfide for Alzheimer's: targeting cholinesterases by in vitro and in silico approaches - Ibrahim_2023_RSC.Adv_13_25379
Author(s) : Ibrahim M , Ali M , Halim SA , Latif A , Ahmad M , Ali S , SameeUllah , Khan A , Rebierio AI , Uddin J , Al-Harrasi A
Ref : RSC Adv , 13 :25379 , 2023
Abstract : In current research, two functional components, i.e., hydrazone and bisphenol sulfide were combined to get useful supramolecules in medicinal chemistry. Herein 25 new 4,4'-thiodiphenol bis-acylhydrazones were synthesized in good to excellent yields. Initially ethyl-2-chloroacetate was reacted with 4,4'-thiodiphenol, which was further reacted with excess hydrazine hydrate to produce 2,2'-((thiobis(4,1-phenylene))bis(oxy))di(acetohydrazide), which was then combined with various aromatic and aliphatic aldehydes to get the desired products (hydrazones, 4a-4y). The synthesized supramolecules were characterized by contemporary spectroscopic techniques such as (1)H NMR, (13)C NMR, and mass spectroscopy. The synthetic compound's cholinesterase blocking activity was tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes where compounds 4n, and 4h showed excellent inhibitory potential for AChE, while 4b, and 4h, demonstrated most potent inhibition of BChE. The starting compound (SM3) and compounds 4h and SM3 depicted excellent dual inhibitory capabilities for both enzymes. The chemical basis of anticholinesterase activity was investigated using a structure-based molecular docking approach. The biological significance and the ease of synthesis of this class of compounds should be considered in therapeutic development for Alzheimer's disease treatments.
ESTHER : Ibrahim_2023_RSC.Adv_13_25379
PubMedSearch : Ibrahim_2023_RSC.Adv_13_25379
PubMedID: 37636505

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 : New multitarget directed benzimidazole-2-thiol-based heterocycles as prospective anti-radical and anti-Alzheimer's agents - Latif_2021_Drug.Dev.Res_82_207
Author(s) : Latif A , Bibi S , Ali S , Ammara A , Ahmad M , Khan A , Al-Harrasi A , Ullah F , Ali M
Ref : Drug Dev Res , 82 :207 , 2021
Abstract : A series of new heterocycles (4-18) was synthesized by the structural modification of benzimidazole-2-thiol (BT, 2-MBI). The structures of the synthesized compounds were confirmed with the help of high-resolution mass spectrometry (HRMS) and (1) HNMR spectroscopy. High inhibitions of the oxidants such as ABTS and DPPH were observed for compounds 9 [IC(50) (s) = 167.4 microM (ABTS), 139.5 microM (DPPH)], 10 [IC(50) (s) = 186.5 microM (ABTS), 155.4 microM (DPPH)], 11 [IC(50) (s) = 286.1 microM (ABTS), 189.1 microM (DPPH)], 12 [IC(50) (s) = 310.8 microM (ABTS), 162.2 microM (DPPH)], 14 [IC(50) (s) = 281.3 microM (ABTS), 205.7 microM (DPPH)], 15 [IC(50) (s) = 284.1 microM (ABTS), 177.3 microM (DPPH)], and 16 [IC(50) (s) = 344.7 microM (ABTS), 270.2 microM (DPPH)] as compared with Ascorbic acid [IC(50) (s) = 340.9 microM (ABTS), 164.3 microM (DPPH)]. The anti-Alzheimer's activity was performed in vitro against cholinesterase enzymes (AChE, BChE). Compound 11 was able to show significant inhibitions [IC(50) (s) = 121.2 microM (AChE), 38.3 microM (BChE)] as against that of galantamine [IC(50) (s) = 139.4 microM (AChE), 40.3 microM (BChE)]. Compound 14 was found as a very good inhibitor of butyrylcholinesterase (IC(50) = 35.4 microM) as compared with standard galantamine. Molecular docking was further performed to investigate the mechanism of anticholinesterase activity.
ESTHER : Latif_2021_Drug.Dev.Res_82_207
PubMedSearch : Latif_2021_Drug.Dev.Res_82_207
PubMedID: 32897587

Title : Evaluation of neuroprotective and anti-amnesic effects of Elaeagnus umbellata Thunb. On scopolamine-induced memory impairment in mice - Nazir_2020_BMC.Complement.Med.Ther_20_143
Author(s) : Nazir N , Zahoor M , Nisar M , Karim N , Latif A , Ahmad S , Uddin Z
Ref : BMC Complement Med Ther , 20 :143 , 2020
Abstract : BACKGROUND: Elaeagnus umbellata is abundantly found in Himalayan regions of Pakistan which is traditionally used to treat various health disorders. However, the experimental evidence supporting the anti-amnesic effect is limited. Therefore the study was aimed to evaluate the prospective beneficial effect of E. umbellata on learning and memory in mice. OBJECTIVES: To assess neuroprotective and anti-amnesic effects of E. umbellata fruit extracts and isolated compounds on the central nervous system. METHODS: Major phytochemical groups present in methanolic extract of E. umbellata were qualitatively determined. The total phenolic and flavonoid contents were also determined in extract/fractions of E. umbellata. On the basis of in vitro promising anticholinesterases (AChE & BChE) and antioxidant activities observed for CHF. Ext and isolated compound-I (Chlorogenic acid = CGA), they were further evaluated for learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Y maze and Novel object recognition using standard procedures. The test sample were further assessed for in vivo anticholinesterases (AChE & BChE) and DPPH free radical scavenging activities in mice brain sample and finally validated by molecular docking study using GOLD software. RESULTS: The extract/fractions and isolated compounds were tested for their anticholinesterase and antioxidant potentials. The CHF. Ext and CGA showed maximum % inhibition of tested cholinesterases and free radicals. The CHF. Ext and CGA reversed the effects of scopolamine in mice. The CHF. Ext and CGA significantly increased the alternate arm returns and % spontaneous alteration performance while escape latency times (second) significantly decreased in Y maze test. The CHF. Ext and CGA significantly increased the time spent with novel object and also increased the discrimination index in the Novel object recognition test. Furthermore, molecular docking was used to validate the mechanism of cholinesterases inhibition of isolated compounds. CONCLUSION: The data obtained from behavioral and biochemical studies (AChE/BChE and DPPH/ABTS inhibition) have shown that E. umbellata possessed significant memory enhancing potency. These results suggest that E. umbellata extract possess potential antiamnesic effects and amongst the isolated compounds, compound I could be more effective anti-amnesic therapeutics. However, further studies are needed to identify the exact mechanism of action.
ESTHER : Nazir_2020_BMC.Complement.Med.Ther_20_143
PubMedSearch : Nazir_2020_BMC.Complement.Med.Ther_20_143
PubMedID: 32397979

Title : Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors - Ahmad_2018_Bioorg.Chem_78_427
Author(s) : Ahmad H , Ahmad S , Ali M , Latif A , Shah SAA , Naz H , Ur Rahman N , Shaheen F , Wadood A , Khan HU , Ahmad M
Ref : Bioorg Chem , 78 :427 , 2018
Abstract : Three new norditerpenoids alkaloids, 1beta-hydroxy,14beta-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, (1)H and (13)C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.
ESTHER : Ahmad_2018_Bioorg.Chem_78_427
PubMedSearch : Ahmad_2018_Bioorg.Chem_78_427
PubMedID: 29698893

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 : Selective dual cholinesterase inhibitors from Aconitum laeve - Ahmad_2017_J.Asian.Nat.Prod.Res__1
Author(s) : Ahmad H , Ahmad S , Shah SAA , Khan HU , Khan FA , Ali M , Latif A , Shaheen F , Ahmad M
Ref : J Asian Nat Prod Res , :1 , 2017
Abstract : New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1-6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1-6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC50 = 3.7 muM, 4.53 muM) and BChE (IC50 = 12.23 muM, 9.94 muM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC50 = 2.51 and 6.13 muM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.
ESTHER : Ahmad_2017_J.Asian.Nat.Prod.Res__1
PubMedSearch : Ahmad_2017_J.Asian.Nat.Prod.Res__1
PubMedID: 28463565

Title : Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution - Pope_2011_PLoS.One_6_e16329
Author(s) : Pope WH , Jacobs-Sera D , Russell DA , Peebles CL , Al-Atrache Z , Alcoser TA , Alexander LM , Alfano MB , Alford ST , Amy NE , Anderson MD , Anderson AG , Ang AA , Ares M, Jr. , Barber AJ , Barker LP , Barrett JM , Barshop WD , Bauerle CM , Bayles IM , Belfield KL , Best AA , Borjon A, Jr. , Bowman CA , Boyer CA , Bradley KW , Bradley VA , Broadway LN , Budwal K , Busby KN , Campbell IW , Campbell AM , Carey A , Caruso SM , Chew RD , Cockburn CL , Cohen LB , Corajod JM , Cresawn SG , Davis KR , Deng L , Denver DR , Dixon BR , Ekram S , Elgin SC , Engelsen AE , English BE , Erb ML , Estrada C , Filliger LZ , Findley AM , Forbes L , Forsyth MH , Fox TM , Fritz MJ , Garcia R , George ZD , Georges AE , Gissendanner CR , Goff S , Goldstein R , Gordon KC , Green RD , Guerra SL , Guiney-Olsen KR , Guiza BG , Haghighat L , Hagopian GV , Harmon CJ , Harmson JS , Hartzog GA , Harvey SE , He S , He KJ , Healy KE , Higinbotham ER , Hildebrandt EN , Ho JH , Hogan GM , Hohenstein VG , Holz NA , Huang VJ , Hufford EL , Hynes PM , Jackson AS , Jansen EC , Jarvik J , Jasinto PG , Jordan TC , Kasza T , Katelyn MA , Kelsey JS , Kerrigan LA , Khaw D , Kim J , Knutter JZ , Ko CC , Larkin GV , Laroche JR , Latif A , Leuba KD , Leuba SI , Lewis LO , Loesser-Casey KE , Long CA , Lopez AJ , Lowery N , Lu TQ , Mac V , Masters IR , McCloud JJ , McDonough MJ , Medenbach AJ , Menon A , Miller R , Morgan BK , Ng PC , Nguyen E , Nguyen KT , Nguyen ET , Nicholson KM , Parnell LA , Peirce CE , Perz AM , Peterson LJ , Pferdehirt RE , Philip SV , Pogliano K , Pogliano J , Polley T , Puopolo EJ , Rabinowitz HS , Resiss MJ , Rhyan CN , Robinson YM , Rodriguez LL , Rose AC , Rubin JD , Ruby JA , Saha MS , Sandoz JW , Savitskaya J , Schipper DJ , Schnitzler CE , Schott AR , Segal JB , Shaffer CD , Sheldon KE , Shepard EM , Shepardson JW , Shroff MK , Simmons JM , Simms EF , Simpson BM , Sinclair KM , Sjoholm RL , Slette IJ , Spaulding BC , Straub CL , Stukey J , Sughrue T , Tang TY , Tatyana LM , Taylor SB , Taylor BJ , Temple LM , Thompson JV , Tokarz MP , Trapani SE , Troum AP , Tsay J , Tubbs AT , Walton JM , Wang DH , Wang H , Warner JR , Weisser EG , Wendler SC , Weston-Hafer KA , Whelan HM , Williamson KE , Willis AN , Wirtshafter HS , Wong TW , Wu P , Yang Y , Yee BC , Zaidins DA , Zhang B , Zuniga MY , Hendrix RW , Hatfull GF
Ref : PLoS ONE , 6 :e16329 , 2011
Abstract : Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.
ESTHER : Pope_2011_PLoS.One_6_e16329
PubMedSearch : Pope_2011_PLoS.One_6_e16329
PubMedID: 21298013
Gene_locus related to this paper: 9caud-g1jvt5 , 9caud-e0ypf9

Title : Calcitonin releases acid phosphatase from rat ventral prostate explants - Latif_1994_Life.Sci_54_561
Author(s) : Latif A , Nakhla AM
Ref : Life Sciences , 54 :561 , 1994
Abstract : Inclusion of salmon calcitonin in the culture medium of rat ventral prostate explants diminished l-tartarate-sensitive acid phosphatase activity in the tissues with a concomitant increment of the enzyme activity in the medium. The effect of the hormone was dose-dependent for a dose range of 10(-12)-10(-6) M. Acid phosphatase activity in prostate explants decreased from 38.6 +/- 3.5 to 20.5 +/- 2.8, whereas it increased from 0.60 +/- 0.15 to 2.80 +/- 0.40 nmol p-nitrophenol liberated/mg protein/30 min in the culture medium. Tissues exposed to 10(-6) M salmon calcitonin had higher acetylcholinesterase activity (8.8 +/- 0.7) than non-exposed ones (6.2 +/- 0.5 mumol substrate hydrolyzed/g tissue/min). These results suggest that locally produced calcitonin causes a release for prostatic acid phosphatase from prostate tissues possibly through its interaction with the cholinergic system.
ESTHER : Latif_1994_Life.Sci_54_561
PubMedSearch : Latif_1994_Life.Sci_54_561
PubMedID: 8107534