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Bacille Calmette-Guérin (BCG) osteomyelitis: a rare complication of BCG vaccination

Venugopal V, Ng DC

BMJ Case Rep, 2024 Sep 10;17(9).
PMID: 39256178 DOI: 10.1136/bcr-2024-261058

The BCG vaccine is considered a safe and efficacious vaccine in the prevention of severe forms of tuberculosis. BCG osteomyelitis is a rare complication of the BCG vaccine that occurs in vaccinated young children. We report a case of BCG osteomyelitis in a male toddler, presenting with painful left wrist swelling without preceding fever or systemic symptoms. Radiographic evidence of osteomyelitis in the left wrist was observed. Initial treatment with conventional antibiotics for acute haematogenous osteomyelitis showed no improvement. The diagnosis of Mycobacterium bovis BCG osteomyelitis was confirmed via tissue samples for histopathological examination and mycobacterial cultures. The patient responded well to treatment with oral antituberculous therapy. This case highlights the importance of considering BCG osteomyelitis in the differential diagnosis of unexplained joint swelling in BCG-vaccinated young children.
Fulltext Targeting cysteine rich C1 domain of Scaffold protein Kinase Suppressor of Ras (KSR) with anthocyanidins and flavonoids - a binding affinity characterization study

Karthik D, Majumder P, Palanisamy S, Khairunnisa K, Venugopal V

Bioinformation, 2014;10(9):580-5.
PMID: 25352726 DOI: 10.6026/97320630010580

Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the core kinase components of the ERK cascade, Raf, MEK, ERK to provide spatial and temporal regulation of Ras-dependent ERK cascade signaling. Interruption of this mechanism can have a high influence in inhibiting the downstream signaling of the mutated tyrosine kinase receptor kinase upon ligand binding. Still none of the studies targeted to prevent the binding of Raf, MEK binding on kinase suppressor of RAS. In that perspective the cysteine rich C1 domain of scaffold proteins kinase suppressor of Ras-1 was targeted rather than its ATP binding site with small ligand molecules like flavones and anthocyanidins and analyzed through insilico docking studies. The binding energy evaluation shows the importance of hydroxyl groups at various positions on the flavone and anthocyanidin nucleus. Over all binding interaction shows these ligands occupied the potential sites of cysteine rich C1 domain of scaffold protein KSR.
Fulltext Green Synthesis and Characterization of Silver Nanoparticles Using Spondias mombin Extract and Their Antimicrobial Activity against Biofilm-Producing Bacteria

Samuggam S, Chinni SV, Mutusamy P, Gopinath SCB, Anbu P, Venugopal V, et al.

Molecules, 2021 May 03;26(9).
PMID: 34063685 DOI: 10.3390/molecules26092681

Multidrug resistant bacteria create a challenging situation for society to treat infections. Multidrug resistance (MDR) is the reason for biofilm bacteria to cause chronic infection. Plant-based nanoparticles could be an alternative solution as potential drug candidates against these MDR bacteria, as many plants are well known for their antimicrobial activity against pathogenic microorganisms. Spondias mombin is a traditional plant which has already been used for medicinal purposes as every part of this plant has been proven to have its own medicinal values. In this research, the S. mombin extract was used to synthesise AgNPs. The synthesized AgNPs were characterized and further tested for their antibacterial, reactive oxygen species and cytotoxicity properties. The characterization results showed the synthesized AgNPs to be between 8 to 50 nm with -11.52 of zeta potential value. The existence of the silver element in the AgNPs was confirmed with the peaks obtained in the EDX spectrometry. Significant antibacterial activity was observed against selected biofilm-forming pathogenic bacteria. The cytotoxicity study with A. salina revealed the LC50 of synthesized AgNPs was at 0.81 mg/mL. Based on the ROS quantification, it was suggested that the ROS production, due to the interaction of AgNP with different bacterial cells, causes structural changes of the cell. This proves that the synthesized AgNPs could be an effective drug against multidrug resistant bacteria.
Fulltext Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities

Venugopal V, Krishnan S, Palanimuthu VR, Sankarankutty S, Kalaimani JK, Karupiah S, et al.

PLoS One, 2018;13(11):e0206109.
PMID: 30408068 DOI: 10.1371/journal.pone.0206109

The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.
Mechanistic insights into the beneficial effects of curcumin on insulin resistance: Opportunities and challenges

Balakumar P, Venkatesan K, Abdulla Khan N, Raghavendra NM, Venugopal V, Bharathi DR, et al.

Drug Discov Today, 2023 Jul;28(7):103627.
PMID: 37224995 DOI: 10.1016/j.drudis.2023.103627

The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities.
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.
Dihydroquinazolin-4(1H)-one derivatives as novel and potential leads for diabetic management

Babatunde O, Hameed S, Salar U, Chigurupati S, Wadood A, Rehman AU, et al.

Mol Divers, 2021 Mar 01.
PMID: 33650031 DOI: 10.1007/s11030-021-10196-5

A variety of dihydroquinazolin-4(1H)-one derivatives (1-37) were synthesized via "one-pot" three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02-88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12-89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure-activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.
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.
New pyrrolopyridine-based thiazolotriazoles as diabetics inhibitors: enzymatic kinetics and in silico study

Taha M, Rahim F, Hayat S, Chigurupati S, Khan KM, Imran S, et al.

Future Med Chem, 2023 Mar;15(5):405-419.
PMID: 37013918 DOI: 10.4155/fmc-2022-0306

Aim: To synthesize pyrrolopyridine-based thiazolotriazoles as a novel class of α-amylase and α-glucosidase inhibitors and to determine their enzymatic kinetics. Methodology: Pyrrolopyridine-based thiazolotriazole analogs (1-24) were synthesized and characterized through proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance and high-resolution electron ionization mass spectrometry. Results: All synthesized analogs displayed good inhibitory potential of α-amylase and α-glucosidase ranging 17.65-70.7 μM and 18.15-71.97 μM, respectively, compared with the reference drug, acarbose (11.98 μM and 12.79 μM). Analog 3 was the most potent among the synthesized analogs, having α-amylase and α-glucosidase inhibitory activity at 17.65 and 18.15 μM, respectively. The structure-activity relationship and binding modes of interactions between selected analogs were confirmed via docking and enzymatic kinetics studies. The compounds (1-24) were tested for cytotoxicity against the 3T3 mouse fibroblast cell line and were observed to be nontoxic.
Synthesis of indole derivatives as diabetics II inhibitors and enzymatic kinetics study of α-glucosidase and α-amylase along with their in-silico study

Taha M, Alrashedy AS, Almandil NB, Iqbal N, Anouar EH, Nawaz M, et al.

Int J Biol Macromol, 2021 Nov 01;190:301-318.
PMID: 34481854 DOI: 10.1016/j.ijbiomac.2021.08.207

In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10-52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.
Fulltext Implementation of a COVID-19 surveillance programme for healthcare workers in a teaching hospital in an upper-middle-income country

Wan KS, Tok PSK, Yoga Ratnam KK, Aziz N, Isahak M, Ahmad Zaki R, et al.

PLoS One, 2021;16(4):e0249394.
PMID: 33852588 DOI: 10.1371/journal.pone.0249394

INTRODUCTION: The reporting of Coronavirus Disease 19 (COVID-19) mortality among healthcare workers highlights their vulnerability in managing the COVID-19 pandemic. Some low- and middle-income countries have highlighted the challenges with COVID-19 testing, such as inadequate capacity, untrained laboratory personnel, and inadequate funding. This article describes the components and implementation of a healthcare worker surveillance programme in a designated COVID-19 teaching hospital in Malaysia. In addition, the distribution and characteristics of healthcare workers placed under surveillance are described.
MATERIAL AND METHODS: A COVID-19 healthcare worker surveillance programme was implemented in University Malaya Medical Centre. The programme involved four teams: contact tracing, risk assessment, surveillance and outbreak investigation. Daily symptom surveillance was conducted over fourteen days for healthcare workers who were assessed to have low-, moderate- and high-risk of contracting COVID-19. A cross-sectional analysis was conducted for data collected over 24 weeks, from the 6th of March 2020 to the 20th of August 2020.
RESULTS: A total of 1,174 healthcare workers were placed under surveillance. The majority were females (71.6%), aged between 25 and 34 years old (64.7%), were nursing staff (46.9%) and had no comorbidities (88.8%). A total of 70.9% were categorised as low-risk, 25.7% were moderate-risk, and 3.4% were at high risk of contracting COVID-19. One-third (35.2%) were symptomatic, with the sore throat (23.6%), cough (19.8%) and fever (5.0%) being the most commonly reported symptoms. A total of 17 healthcare workers tested positive for COVID-19, with a prevalence of 0.3% among all the healthcare workers. Risk category and presence of symptoms were associated with a positive COVID-19 test (p<0.001). Fever (p<0.001), cough (p = 0.003), shortness of breath (p = 0.015) and sore throat (p = 0.002) were associated with case positivity.
CONCLUSION: COVID-19 symptom surveillance and risk-based assessment have merits to be included in a healthcare worker surveillance programme to safeguard the health of the workforce.

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