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Fulltext Validation and clinical interpretation of the St George's respiratory questionnaire for COPD (SGRQ-C) after adaptation to Malaysian language and culture, in patients with COPD

Rehman AU, Hassali MAA, Harun SN, Abbas S, Muneswarao J, Ali IABH, et al.

Health Qual Life Outcomes, 2020 May 13;18(1):138.
PMID: 32404113 DOI: 10.1186/s12955-020-01393-1

BACKGROUND: Cultural differences affect the administration and results of health status questionnaires. "Cross cultural adaptation" ensures retention of psychometric properties such as validity and reliability at an item and/or scale level.
OBJECTIVE: To develop a Malaysian version of St George's respiratory COPD specific questionnaire (SGRQ-CM), to evaluate the full spectrum of psychometric properties (reliability, validity and responsiveness), to test the factor structure and to assess minimum clinically important difference for the SGRQ-CM, to be used in population of Malaysia.
METHODOLOGY: SGRQ-C was translated to Bahasa Malaysia using a standard protocol. 240 COPD patients were included in the study. All patients were followed-up for six months. Construct validity, internal consistency, item convergent validity, test-retest ability, responsiveness, factor analysis and MCID of the Malaysian version of SGRQ-C to be used in population of Malaysia were evaluated.
RESULTS: The Cronbach alpha coefficient and intraclass correlation coefficients (ICC) for SGRQ-CM were reported as 0.87, and 0.88 respectively. Correlation of SGRQ-CM with CAT, EQ-5D-5 L, mMRC dyspnea scales and FEV1%predicted were reported as 0.86, - 0.82, 0.72 and - 0.42 respectively. Correlation coefficient between the subscales and other clinical and health status measures ranged from r = - 0.35 to r = - 0.87. The MCID was reported as 5.07 (- 2.54-12.67).
CONCLUSION: The Malaysian version of SGRQ-C has a good psychometric property comparable to those of the original version and has a strong evidence of validity, reliability and responsiveness towards disease severity in Malaysian COPD patients. It can be recommended as a reliable quality of life measure for future research.
Fulltext Tuberculosis (TB) treatment challenges in TB-diabetes comorbid patients: a systematic review and meta-analysis

Khattak M, Rehman AU, Muqaddas T, Hussain R, Rasool MF, Saleem Z, et al.

Ann Med, 2024 Dec;56(1):2313683.
PMID: 38346381 DOI: 10.1080/07853890.2024.2313683

BACKGROUND: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme.
METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results.
RESULTS: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p
Fulltext Toxicological Screening of 4-Phenyl-3,4-dihydrobenzo[h]quinolin-2(1H)-one: A New Potential Candidate for Alzheimer's Treatment

Anwar F, Saleem U, Rehman AU, Ahmad B, Ismail T, Mirza MU, et al.

ACS Omega, 2021 Apr 27;6(16):10897-10909.
PMID: 34056243 DOI: 10.1021/acsomega.1c00654

Toxicity studies are necessary for the development of a new drug. Naphthalene is a bicyclic molecule and is easy to derivatize. In our previous study, a derivative of naphthalene (4-phenyl,3,4-dihydrobenzoquinoline-2(H)one) was synthesized and reported its in vitro activity on different enzymes. This study was a probe to investigate the toxicity potential of that compound (SF3). Acute oral (425), subacute (407), and teratogenicity (414) studies were planned according to their respective guidelines given by organization of economic cooperation and development (OECD). Acute oral, subacute, and teratogenicity studies were carried out on 2000, 5-40, and 40 mg/kg doses. Blood samples were collected for hematological and biochemical analyses. Vital organs were excised for oxidative stress (superoxide dismutase, catalase, glutathione, and malondialdehyde) and histopathological analysis. LD 50 of SF3 was higher than 2000 mg/kg. In acute and subacute studies, levels of alkaline phosphates and aspartate transaminase were increased. Teratogenicity showed no resorptions, no skeletal or soft tissue abnormalities, and no cleft pallet. Oxidative stress biomarkers were close to the normal, and no increase in the malondialdehyde level was seen. Histopathological studies revealed normal tissue architecture of the selected organs, except kidney, in acute oral and subacute toxicity studies at 40 mg/kg. The study concluded that SF3 is safer if used as a drug.
Fulltext Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar F, Saleem U, Rehman AU, Ahmad B, Froeyen M, Mirza MU, et al.

Front Pharmacol, 2021;12:607026.
PMID: 34040515 DOI: 10.3389/fphar.2021.607026

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD
50
. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.
Fulltext The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis

Rehman AU, Khattak M, Mushtaq U, Latif M, Ahmad I, Rasool MF, et al.

Front Public Health, 2023;11:1244450.
PMID: 38074769 DOI: 10.3389/fpubh.2023.1244450

BACKGROUND: The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression.
AIM: To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients.
METHODOLOGY: The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process.
RESULTS: Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p
Fulltext The frequency of pulmonary hypertension in newborn with intrauterine growth restriction

Abbas G, Shah S, Hanif M, Shah A, Rehman AU, Tahir S, et al.

Sci Rep, 2020 05 15;10(1):8064.
PMID: 32415157 DOI: 10.1038/s41598-020-65065-2

Intrauterine growth restriction (IUGR) is a clinical definition applied to neonates born with clinical features of malnutrition and in-utero growth retardation irrespective of their birth weight percentile. This study was aimed to determine the frequency of pulmonary hypertension (PH) in neonates with IUGR. In this descriptive cross-sectional study, we followed 96 neonates with IUGR (≤28 days) and 38 neonates without IUGR born in the department of the neonatal intensive care unit children hospital complex Multan, Pakistan. We analyzed certain factors such as gender, gestational age (GA) (weeks), birth weight (BW in kg), weight percentile (WP) for GA, meconium aspiration syndrome (MAS), birth asphyxia (BA) and respiratory distress syndrome (RDS) for pulmonary hypertension (PH) in IUGR and non-IUGR group. GA was measured by the Ballard scoring system. Echocardiography was performed for all patients by the pediatric cardiologist to measure pulmonary arterial (PA) pressure using Bernoulli's equation. Out of total 96 IUGR neonates, 33.3% (n = 32) suffered from PH, of which 65.3% (n = 18) were male and 43.7% (n = 14) were female. The percentages of IUGR neonates with BA, MAS and RDS were 34.4%, 18.8% and 22.9% respectively. The data were analyzed using the SPSS-16 software to test the statistical significance of the results. A p-value less than 0.05 was considered significant. When the chi-square test was applied, it depicted that MAS was significantly associated with PH in IUGR neonates (p = 0.0001) compared to non-IUGR neonates. Our findings suggested an increased chance of PH in IUGR neonates and MAS may be a strong factor.
The economic burden of chronic obstructive pulmonary disease (COPD) in Europe: results from a systematic review of the literature

Rehman AU, Hassali MAA, Muhammad SA, Harun SN, Shah S, Abbas S

Eur J Health Econ, 2020 Mar;21(2):181-194.
PMID: 31564007 DOI: 10.1007/s10198-019-01119-1

OBJECTIVES: To find the economic burden of COPD and to identify the key cost drivers in the management of COPD patients across different European countries.
BACKGROUND: COPD is a major cause of mortality and morbidity and is associated with considerable economic burden on the individual and society. It limits the daily activities and working ability of the patients.
METHODOLOGY: We conducted a systematic search of PUBMED, SCIENCE DIRECT, Cochrane CENTRAL, SCOPUS, Google Scholar and SAGE Premier Databases to find scientific research articles evaluating the cost of COPD management from patient and societal perspective.
RESULTS: Estimated per patient per year direct cost in Norway, Denmark, Germany, Italy, Sweden, Greece, Belgium, and Serbia was €10,701, €9580, €7847, €7448, €7045, €2896, €1963, and €2047, respectively. Annual per patient cost of work productivity loss was highest in Germany as €5735 and lowest in Greece as €998. It was estimated as €4824, €2033 and €1298 in Bulgaria, Denmark and Sweden, respectively. Several factors found associated with increasing cost of COPD management that include but not limited to late diagnosis, severity of disease, frequency of exacerbation, hospital readmissions, non-adherence to the therapy and exposure to COPD risk factors.
CONCLUSION: Minimizing the COPD exacerbations and controlling the worsening of symptoms may potentially reduce the cost of COPD management at any stage.
Synthesis, α-glucosidase inhibitory, cytotoxicity and docking studies of 2-aryl-7-methylbenzimidazoles

Taha M, Ismail NH, Imran S, Mohamad MH, Wadood A, Rahim F, et al.

Bioorg Chem, 2016 Apr;65:100-9.
PMID: 26894559 DOI: 10.1016/j.bioorg.2016.02.004

Benzimidazole analogs 1-27 were synthesized, characterized by EI-MS and (1)HNMR and their α-glucosidase inhibitory activities were found out experimentally. Compound 25, 19, 10 and 20 have best inhibitory activities with IC50 values 5.30±0.10, 16.10±0.10, 25.36±0.14 and 29.75±0.19 respectively against α-glucosidase. Compound 6 and 12 has no inhibitory activity against α-glucosidase enzyme among the series. Further studies showed that the compounds are not showing any cytotoxicity effect. The docking studies of the compounds as well as the experimental activities of the compounds correlated well. From the molecular docking studies, it was observed that the top ranked conformation of all the compounds fit well in the active site of the homology model of α-glucosidase.
Synthesis, in vitro biological screening and docking study of benzo[d]oxazole bis Schiff base derivatives as a potent anti-Alzheimer agent

Taha M, Rahim F, Zaman K, Anouar EH, Uddin N, Nawaz F, et al.

J Biomol Struct Dyn, 2023 Mar;41(5):1649-1664.
PMID: 34989316 DOI: 10.1080/07391102.2021.2023640

We have synthesized benzo[d]oxazole derivatives (1-21) through a multistep reaction. Alteration in the structure of derivatives was brought in the last step via using various substituted aromatic aldehydes. In search of an anti-Alzheimer agent, all derivatives were evaluated against acetylcholinesterase and butyrylcholinesterase enzyme under positive control of standard drug donepezil (IC50 = 0.016 ± 0.12 and 4.5 ± 0.11 µM) respectively. In case of acetylcholinesterase enzyme inhibition, derivatives 8, 9 and 18 (IC50 = 0.50 ± 0.01, 0.90 ± 0.05 and 0.3 ± 0.05 µM) showed very promising inhibitory potentials. While in case of butyrylcholinesterase enzyme inhibition, most of the derivatives like 6, 8, 9, 13, 15, 18 and 19 (IC50 = 2.70 ± 0.10, 2.60 ± 0.10, 2.20 ± 0.10, 4.25 ± 0.10, 3.30 ± 0.10, 0.96 ± 0.05 and 3.20 ± 0.10 µM) displayed better inhibitory potential than donepezil. Moreover, derivative 18 is the most potent one among the series in both inhibitions. The binding interaction of derivatives with the active gorge of the enzyme was confirmed via a docking study. Furthermore, the binding interaction between derivatives and the active site of enzymes was correlated through the SAR study. Structures of all derivatives were confirmed through spectroscopic techniques such as 1H-NMR, 13C-NMR and HREI-MS, respectively.Communicated by Ramaswamy H. Sarma.
Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles

Rafique R, Khan KM, Arshia, Chigurupati S, Wadood A, Rehman AU, et al.

Bioorg Chem, 2020 01;94:103410.
PMID: 31732193 DOI: 10.1016/j.bioorg.2019.103410

Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC50 = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ± 0.09 µM, and IC50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.
Synthesis, in vitro urease inhibitory potential and molecular docking study of Benzimidazole analogues

Zaman K, Rahim F, Taha M, Ullah H, Wadood A, Nawaz M, et al.

Bioorg Chem, 2019 08;89:103024.
PMID: 31176853 DOI: 10.1016/j.bioorg.2019.103024

Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the urease inhibitory potential. For that purpose, benzimidazole analogues 1-19 were synthesized and screened for in vitro urease inhibitory potential. Structures of all synthetic analogues were deduced by different spectroscopic techniques. All analogues revealed inhibition potential with IC50 values of 0.90 ± 0.01 to 35.20 ± 1.10 μM, when compared with the standard thiourea (IC50 = 21.40 ± 0.21 μM). Limited SAR suggested that the variations in the inhibitory potentials of the analogues are the result of different substitutions on phenyl ring. In order to rationalize the binding interactions of most active compounds with the active site of urease enzyme, molecular docking study was conducted.
Synthesis, in vitro evaluation and molecular docking studies of biscoumarin thiourea as a new inhibitor of α-glucosidases

Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F, et al.

Bioorg Chem, 2015 Dec;63:36-44.
PMID: 26432614 DOI: 10.1016/j.bioorg.2015.09.004

Biscoumarin analogs 1-18 have been synthesized, characterized by EI-MS and (1)H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5±0.39 and 104.62±0.3μM when compared with standard acarbose having IC50 value 774.5±1.94μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1-18 are new. Our synthesized compounds can further be studied to developed lead compounds.
Fulltext Synthesis, Kinetics, Binding Conformations and Structure-activity Relationship of Potent Tyrosinase Inhibitors: Aralkylated 2-aminothiazole-ethyltriazole Hybrids

Sadiq Butt AR, Abbasi MA, Rehman AU, Siddiqui SZ, Raza H, Hassan M, et al.

Iran J Pharm Res, 2021;20(2):206-228.
PMID: 34567157 DOI: 10.22037/ijpr.2020.15521.13145

Considering the diversified pharmacological importance of thiazole and triazole heterocyclic moieties, a unique series of S-aralkylated bi-heterocyclic hybrids, 7a-l, was synthesized in a convergent manner. The structures of newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, IR, and EI-MS spectral studies. The structure-activity relationship of these compounds was envisaged by analyzing their inhibitory effects against tyrosinase, whereby all these molecules exhibited potent inhibitory potentials relative to the standard used. The Kinetics mechanism was ascertained by Lineweaver-Burk plots, which revealed that 7g inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0057µM. These bi-heterocyclic molecules also disclosed good binding energy values (kcal /mol) when assessed computationally. So, these molecules can be considered promising medicinal scaffolds for the treatment of skin disorders.
Synthesis, Antioxidant and In-Silico Studies of Potent Urease Inhibitors: N-(4-{[(4-Methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides

Abbasi MA, Raza H, Rehman AU, Siddiqui SZ, Nazir M, Mumtaz A, et al.

Drug Res (Stuttg), 2019 Feb;69(2):111-120.
PMID: 30086567 DOI: 10.1055/a-0654-5074

In this study, a new series of sulfonamides derivatives was synthesized and their inhibitory effects on DPPH and jack bean urease were evaluated. The in silico studies were also applied to ascertain the interactions of these molecules with active site of the enzyme. Synthesis was initiated by the nucleophilic substitution reaction of 2-(4-methoxyphenyl)-1-ethanamine (1: ) with 4-(acetylamino)benzenesulfonyl chloride (2): in aqueous sodium carbonate at pH 9. Precipitates collected were washed and dried to obtain the parent molecule, N-(4-{[(4-methoxyphenethyl)amino]sulfonyl}phenyl)acetamide (3): . Then, this parent was reacted with different alkyl/aralkyl halides, (4A-M: ), using dimethylformamide (DMF) as solvent and LiH as an activator to produce a series of new N-(4-{[(4-methoxyphenethyl)-(substituted)amino]sulfonyl}phenyl)acetamides (5A-M: ). All the synthesized compounds were characterized by IR, EI-MS, 1H-NMR, 13C-NMR and CHN analysis data. All of the synthesized compounds showed higher urease inhibitory activity than the standard thiourea. The compound 5 F: exhibited very excellent enzyme inhibitory activity with IC50 value of 0.0171±0.0070 µM relative to standard thiourea having IC50 value of 4.7455±0.0546 µM. Molecular docking studies suggested that ligands have good binding energy values and bind within the active region of taget protein. Chemo-informatics properties were evaluated by computational approaches and it was found that synthesized compounds mostly obeyed the Lipinski' rule.
Fulltext Synthesis, Antibacterial and Lipoxygenase Inhibition Studies of N-(Alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamides

Abbasi MA, Rehman AU, Siddiqui SZ, Sheeza A, Nazir S, Ahmad I, et al.

Turk J Pharm Sci, 2017 Apr;14(1):49-55.
PMID: 32454594 DOI: 10.4274/tjps.84756

Objectives: The present research work was aimed to synthesize some new sulfonamides bearing 1,4-benzodioxin ring, which might have suitable antibacterial potential and can be used as possible therapeutic agents for inflammatory ailments.
Materials and Methods: The synthesis was accomplished by the reaction of 2,3-dihydro-1,4-benzodioxin-6-amine (1) with 4-methylbenzenesulfonyl chloride (2) using 10% aqueous Na2CO3 to afford N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamide (3). Further the parent molecule 3 was reacted with different alkyl/aralkyl halides (4a-e) to achieve N-(alkyl/aralkyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamides (5a-e), using polar aprotic solvent; N,N-dimethylformamide (DMF) and catalytic amount of lithium hydride as base. The characterization of synthesized compounds was conducted by contemporary spectral techniques e.g., IR, 1H-NMR and EI-MS. Then these molecules were subjected to screening against various bacterial strains and their inhibitory potential against Lipoxygenase was also ascertained.
Results: The screening results against various Gram-positive and Gram-negative bacterial strains revealed that N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamide (3), N-(2-bromoethyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamide (5a) and N-(2-phenethyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamide (5b) showed good inhibitory activity as compared to standard Ciprofloxacin. Moreover, N-(3-phenylpropyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfonamide (5c) and N-(4-chlorobenzyl)-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-4-methylbenzenesulfon-amide (5e) displayed decent inhibition against lipoxygenase enzyme relative to standard Baicalein.
Conclusion: On the basis of results obtained it can be concluded that the synthesized sulfonamides may provide an overall indispensable basis to introduce new drug candidates for the cure of inflammatory and other associated diseases.
Synthesis of some new N-(alkyl/aralkyl)-N-(4-methoxyphenethyl) benzene sulfonamides as antibacterial agents against Escherichia

Abbasi MA, Fatima Z, Rehman AU, Siddiqui SZ, Ali Shah SA, Shahid M, et al.

Pak J Pharm Sci, 2019 Sep;32(5):1957-1964.
PMID: 31813858

The present study comprises the synthesis of a new series of benzenesulfonamides derived from N-sulfonation of 2-(4-methoxyphenyl)-1-ethanamine (1). The synthesis was initiated by the reaction of 2-(4-methoxyphenyl)-1-ethanamine (1) with benzenesulfonyl chloride (2), to yield N-(4-methoxyphenethyl)benzenesulfonamide (3). This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides (4a-j) in N,N-dimethylformamide (DMF) and in the presence of a weak base lithium hydride (LiH) to obtain various N-(alkyl/aralkyl)-N-(4-methoxyphenethyl) benzenesulfonamides (5a-j). The characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. Elemental analysis also supported this data. The biofilm inhibitory action of all the synthesized compounds was carried out on Escherichia coli and some of the compounds were identified to be very suitable inhibitors of this bacterial strain. Furthermore, the molecules were also tested for their cytotoxicity behavior to assess their utility as less cytotoxic therapeutic agents.
Synthesis of new indazole based dual inhibitors of α-glucosidase and α-amylase enzymes, their in vitro, in silico and kinetics studies

Rafique R, Khan KM, Arshia, Kanwal, Chigurupati S, Wadood A, et al.

Bioorg Chem, 2020 01;94:103195.
PMID: 31451297 DOI: 10.1016/j.bioorg.2019.103195

The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies

Hameed S, Kanwal, Seraj F, Rafique R, Chigurupati S, Wadood A, et al.

Eur J Med Chem, 2019 Dec 01;183:111677.
PMID: 31514061 DOI: 10.1016/j.ejmech.2019.111677

Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 μM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ± 1.31 μM), (IC50 = 2.5 ± 1.21 μM), 36 (IC50 = 2.12 ± 1.35 μM), (IC50 = 2.21 ± 1.08 μM), and 37 (IC50 = 2.00 ± 1.22 μM), (IC50 = 2.04 ± 1.4 μM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.
Sero-epidemiology and risk factor analysis of human brucellosis in Punjab, Pakistan: a cross sectional study

Nawaz Z, Shafique M, Zahoor MA, Siddique AB, Ali S, Arshad R, et al.

Trop Biomed, 2021 Sep 01;38(3):413-419.
PMID: 34608115 DOI: 10.47665/tb.38.3.084

Human brucellosis is a neglected zoonotic problem worldwide with a high degree of morbidity in humans and is mostly overlooked due to other febrile conditions. The aim of this study was to evaluate the sero-prevalence and risk factors of human brucellosis among subjects living in Punjab, Pakistan. In this cross-sectional study, human blood samples were collected from seven districts of Punjab, Pakistan. Information regarding personal data, demographic data and potential risk factors was collected through a structured questionnaire. Detection of anti-Brucella antibodies was done through Rose Bengal Plate Test (RBPT) and Enzyme Linked Immunosorbent Assay (ELISA). Descriptive analysis, Chi square test and Odds ratio was applied using STATA software version 12. The sero-prevalence of human brucellosis was 13.13% with significantly higher percentage in males 17.23% and age group 25-40 years 16.50% (P=< 0.001). The demographic factors positively associated with human brucellosis were lack of education (P = 0.003; OR = 1.85) and farming as an occupation (P =<0.001; OR = 2.50) Similarly, among the risk factors studied, keeping animals at home (P =<0.001; OR = 2.03), slaughtering of animals (P =<0.001; OR = 15.87) and consuming raw milk (P =<0.001; OR = 5.42) were the factors strongly connected with human brucellosis. A massive awareness should be given to livestock farmers and individuals directly linked to animals regarding risk factors and transmission of brucellosis. Consumption of unpasteurized milk and its products should be condemned to curtail this neglected disease.
Fulltext Risk Factors Associated With Medication Errors Among Patients Suffering From Chronic Disorders

Rasool MF, Rehman AU, Imran I, Abbas S, Shah S, Abbas G, et al.

Front Public Health, 2020;8:531038.
PMID: 33330300 DOI: 10.3389/fpubh.2020.531038

Introduction: Medication error is unintentional and can be reduced by reducing the risk factors. Patients suffering from chronic diseases are at an increased risk of medication errors. Objective: This work aims to assess the risk factors associated with medication errors among patients suffering from chronic disorders in hospitals of South Punjab, Pakistan. Methodology: Multiple logistic regression analysis was used to assess the impact of different risk factors on the prevalence of medication errors in patients suffering from chronic diseases. Results: A greater risk for the occurrence of medication errors was associated with age ≥60 years (odds ratio, OR = 1.9; 95% CI = 1.3-3.1; p = 0.001), overburdened healthcare system (OR = 2.2; 95% CI = 1.64-3.56; p < 0.000), number of prescribed drugs ≥5 (OR = 1.74; 95% CI = 1.02-2.64; p < 0.000), comorbidities (OR = 2.6; 95% CI = 1.72-3.6; p = 0.003), Charlson comorbidity index (OR = 1.31; 95% CI = 0.49-1.84; p = 0.004), and multiple prescribers to one patient (OR = 1.12; 95% CI = 0.64-1.76; p = 0.001). Conclusion: Older age, overburdened healthcare system, number of prescribed drugs, comorbidities, Charlson comorbidity index, and multiple prescribers to one patient are significant risk factors for the occurrence of medication errors.

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