The coronavirus disease that outbreak in 2019 has caused various health issues. According to the WHO, the first positive case was detected in Bangladesh on 7th March 2020, but while writing this paper in June 2021, the total confirmed, recovered, and death cases were 826922, 766266 and 13118, respectively. Due to the emergence of COVID-19 in Bangladesh, the country is facing a major public health crisis. Unfortunately, the country does not have a comprehensive health policy to address this issue. This makes it hard to predict how the pandemic will affect the population. Machine learning techniques can help us detect the disease's spread. To predict the trend, parameters, risks, and to take preventive measure in Bangladesh; this work utilized the Recurrent Neural Networks based Deep Learning methodologies like LongShort-Term Memory. Here, we aim to predict the epidemic's progression for a period of more than a year under various scenarios in Bangladesh. We extracted the data for daily confirmed, recovered, and death cases from March 2020 to August 2021. The obtained Root Mean Square Error (RMSE) values of confirmed, recovered, and death cases indicates that our result is more accurate than other contemporary techniques. This study indicates that the LSTM model could be used effectively in predicting contagious diseases. The obtained results could help in explaining the seriousness of the situation, also mayhelp the authorities to take precautionary steps to control the situation.
In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked.
Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.
The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
A new series of oxadiazole with thiadiazole moiety (6-27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard d-saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition.
In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1-25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization.
Alpha-amylase and urease enzyme over expression endorses various complications like rheumatoid arthritis, urinary tract infection, colon cancer, metabolic disorder, cardiovascular risk, and chronic kidney disease. To overcome these complications, we have synthesized new arylhydrazide bearing Schiff bases/thiazolidinone analogues as α-amylase and urease inhibitors. The analogues 1a-r were evaluated for α-amylase inhibitory potential. All analogues were found active and show IC50 value ranging between 0.8 ± 0.05 and 12.50 ± 0.5 μM as compare to standard acarbose (IC50 = 1.70 ± 0.10 μM). Among the synthesized analogs, compound 1j, 1r, 1k, 1e, 1b and 1f having IC50 values 0.8 ± 0.05, 0.9 ± 0.05, 1.00 ± 0.05, 1.10 ± 0.10, 1.20 ± 0.10 and 1.30 ± 0.10 μM respectively showed an excellent inhibitory potential. Analogs 2a-o were evaluated against urease activity. All analogues were found active and show IC50 value ranging between 4.10 ± 0.02 and 38.20 ± 1.10 μM as compare to standard thiourea (IC50 = 21.40 ± 0.21 μM). Among the synthesized analogs, compound 2k, 2a, 2h, 2j, 2f, 2e, 2g, 2b and 2l having IC50 values 4.10 ± 0.02, 4.60 ± 0.02, 4.70 ± 0.03, 5.40 ± 0.02, 6.70 ± 0.05, 8.30 ± 0.3, 11.20 ± 0.04, 16.90 ± 0.8 and 19.80 ± 0.60 μM respectively showed an excellent inhibitory potential. All compounds were characterized through 1H, 13C NMR and HR-EIMS analysis. Structure activity relationship of the synthesized analogs were recognized and confirmed through molecular docking studies.
A series of twenty-six analogs of benzimidazole based oxadiazole have been synthesized and evaluated against alpha-glycosidase enzyme. Most the analogs showed excellent to good inhibitory potential. Among the screened analogs, analog 1, 2, 3 and 14 with IC50 values 4.6 ± 0.1, 9.50 ± 0.3, 2.6 ± 0.1 and 9.30 ± 0.4 µM respectively showedexcellent inhibitory potential than reference drug acarbose (IC50 = 38.45 ± 0.80 µM). Some of the analogs like 19, 21, 22 and 23 with methyl and methoxy substituent on phenyl ring show hydrophobic interaction and were found with no inhibitory potential. The binding interactions between synthesized analogs and ligands protein were confirmed through molecular docking study. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. These derivatives were synthesized by simple mode of synthesis like heterocyclic ring formation.
We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a-j) and 13 benzimidazole-based Schiff bases 2 (a-m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a-j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a-m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.
Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.
We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.
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.
Usnic acid (UA) lately piqued the interest of researchers for its extraordinary biological characteristics, including anticancer activity. Here, the mechanism was clarified through network pharmacology,molecular docking and molecular dynamic simulation. Sixteen proteins were selected through network pharmacology study as they are probable to interact with UA. Out of these proteins, 13 were filtered from PPI network analysis based on their significance of interactions (p
New triazinoindole bearing thiazole/oxazole analogues (1-21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.
A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1HNMR, 13C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC50 = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors.
Voglibose and acarbose are distinguished α-glucosidase inhibitors used for controlling of diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still needed to develop safer therapy. Despite of a broad spectrum of biological importance of benzimidazole, it is occasionally evaluated for α-glucosidase activity. Current study deals with the synthesis and biological screening of benzimidazole bearing bis-Schiff bases (1-19) for their α-glucosidase inhibitory activity. All analogues exhibited excellent to good inhibitory potential (IC50 = 2.20 ± 0.1to 88.60 ± 1.70 µM) when compared with standard drug acarbose (IC50 = 38.45 ± 0.80 µM). A structure activity relationship has been established on the basis of electronic effects and position of different substituents present on phenyl ring. In order to rationalize the binding interactions of most active analogues with the active site of α-glucosidase enzyme, molecular docking study was conducted.
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.
In search of potent urease inhibitor indole analogues (1-22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1-22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed.Communicated by Ramaswamy H. Sarma.
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.
Monkeypox (MPX) is a zoonotic disease caused by the MPX virus from the poxviridae family of orthopoxviruses. Typically, endemic in central and west Africa, it has now become a matter of concern since cases have been reported in non-endemic countries around mid-June 2022, especially in the European region, with the transmission not related to travel. The diagnosis is made by PCR testing of the skin lesions. Even though treatment is symptomatic, antiretrovirals, such as tecovirimat, are used in severe cases. Vaccination with second and third generation vaccines is approved for prophylaxis in high risk individuals. Unfortunately, these options of treatment and prevention are only available in high income countries at the moment. This review, through a thorough literature search of articles from 2017 onward, focuses on epidemiology, clinical manifestations, challenges, treatment, prevention and control of MPX virus and how they can be corelated with other viral outbreaks including COVID-19, Acute Hepatitis of unknown origin, Measles and Dengue, to better predict and therefore prevent its transmission. The previous COVID-19 pandemic increased the disease burden on healthcare infrastructure of low-middle income countries, therefore, this recent MPX outbreak calls for a joint effort from healthcare authorities, political figures, and NGOs to combat the disease and prevent its further spread not only in high income but also in middle- and low-income countries.