Intestinal viral infections of nSARS-CoV2 in the Indian community: Risk of virus spread in India.

In December 2019, novel severe acute respiratory syndrome coronavirus 2 (nSARS-CoV-2) virus outbreaks emerged from Wuhan, China, and spread all over the world, including India. Molecular diagnosis of Coronavirus Disease 2019 (COVID) 19 for densely and highly populated countries like India is time-consuming. A few reports have described the successful diagnosis of nSARS-CoV-2 virus from sewage and wastewater samples contaminated with fecal matter, suggesting the diagnosis of COVID 19 from the same to raise an alarm about the community transmission of virus for implementation of evacuation and lockdown strategies. So far, the association between the detection of virus and its concentration in stool samples with severity of the disease and the presence or absence of gastrointestinal symptoms have been rarely reported. We led the search utilizing multiple databases, specifically PubMed (Medline), EMBASE, and Google Scholar. We conducted a literature survey on gastrointestinal infection and the spread of this virus through fecal-oral transmission. Reports suggested that the existence and persistence of nSARS-CoV-2 in anal/rectal swabs and stool specimens for a longer period of time than in nasopharyngeal swabs provides a strong tenable outcome of gastrointestinal contamination and dissemination of this infection via potential fecal-oral transmission. This review may be helpful to conduct further studies to address the enteric involvement and excretion of nSARS-CoV-2 RNA in feces and control the community spread in both COVID-19 patients ahead of the onset of symptoms and in asymptomatic individuals through wastewater and sewage surveillance as an early indication of infection. The existence of the viral genome and active viral particle actively participate in genomic variations. Hence, we comprehended the enteric spread of different viruses amongst communities with special reference to nSARS-CoV-2.

Is white the right light for the clinical electrooculogram?

PURPOSE: To investigate if a lower luminance monochromatic LED stimulus could be used as an alternative to a high luminance white light for the clinical electrooculogram. METHODS: Clinical electrooculograms were recorded in color normal participants (N = 23) aged 22.6 ± 1.2 years, 7 male and 16 female using the standard 100 cd.m-2 white illuminant and four monochromatic LEDs with peak wavelengths of 448, 534, 596 and 634 nm at 30 cd.m-2. Pupils were dilated and there was a 30 cd.m-2pre-adaptation to white light for 2 min followed by 15 min dark adaptation and 20 min recording in the light stimulus using a Ganzfeld stimulator. RESULTS: The normalized LP:DTratio for the short wavelength LED (448 nm) was equivalent in amplitude and timing to the ISCEV standard EOG (p = .99). The LP:DTratio for the white (100 cd.m-2) and 448 nm (30 cd.m-2) were (median ± SEM): 2.49 ± .11 and 2.47 ± .11. The time to light-rise peak was also equivalent being 9.0 ± .2 and 8.0 ± .4 min (p = .54). CONCLUSIONS: Consideration may be given to using a short wavelength monochromatic stimulus that is more comfortable for the subject than the current 100 cd.m-2 illuminant.

Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: Synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment.

A series of new benzothiazole-1,3,4-oxadiazole-4-thiazolidinone hybrid analogs (Tz1-Tz28) were synthesized in search of potential anti-diabetic agents. Molecular docking study was conducted with binding pocket of peroxisome proliferator activated receptor-gamma to elucidate the binding interactions of newly synthesized targets. Seven selected compounds with best docking scores were further screened for in vivo anti-hyperglycemic efficacy by oral glucose tolerance test in non-diabetic rats and on streptozotocin induced diabetic rat models. All the tested compounds demonstrated excellent to moderate reduction in blood glucose levels. Three of the compounds (Tz21, Tz7 and Tz10) showed excellent anti-diabetic effect by reducing concentration of glucose to 157.15 ±â€¯1.79 mg/dL, 154.39 ±â€¯1.71 mg/dL, 167.36 ±â€¯2.45 mg/dL, respectively better than the standard drug, pioglitazone, 178.32 ±â€¯1.88 mg/dL. Moreover, three derivatives Tz21, Tz4 and Tz24 with IC50 values of 0.21 ±â€¯0.01 µM, 9.03 ±â€¯0.12 µM and 11.96 ±â€¯0.40 µM respectively also showed better inhibitory activities on alpha-glucosidase even more than the standard acarbose (IC50 = 18.5 ±â€¯0.20 µM), indicating Tz21 has the highest inhibitory effect among the seven tested derivatives. Prediction of Drug like properties using molinspiration online software suggests that all the synthesized compounds have potential of becoming the orally active molecules. Thus, these novel hybrids could serve as potential candidates to become leads for the development of new drugs eliciting anti-hyperglycemic effect orally.

Synthesis, ADME, docking studies and in vivo anti-hyperglycaemic potential estimation of novel Schiff base derivatives from octadec-9-enoic acid.

A new series of octadec-9-enoic acid schiff base entities (S1-S30) were designed and synthesized targeting peroxisome proliferator activated receptor-gamma for agonist action. Molinspiration software (online) was used to estimate drug like molecular properties of the metabolites. Docking disquisition on co-crystallized protein of PPAR-γ (PDB ID 1FM9) was carried out which showed S21, S10 and S7 as best situated in the vital sites of receptor having docking scores -9.19, -8.68 and -8.64 respectively. Free binding energy measured using model of Maestro 9.0 and was in range of from -40.01 and -80.54 kcal/mol, significant when compared with pioglitazone (-51.58 Kcal/mol). Seven best docked derivatives were assessed for in-vivo oral glucose tolerance on normal rats and anti-hyperglycaemic activity by streptozotocin induced diabetes model. S21 unveiled to be the best measured analogue among all the synthesized entities. Encouraging outcomes motivates fatty acids for further development of more effective and safer compounds.

Synthesis, molecular modelling studies and ADME prediction of benzothiazole clubbed oxadiazole-Mannich bases, and evaluation of their anti-diabetic activity through in vivo model.

A small library of new benzothiazole clubbed oxadiazole-Mannich bases (M-1 to M-22) were synthesized and characterized by IR, NMR, Mass and Elemental analysis results. Molecular docking studies were done to assess the binding mode and interactions of synthesized hits at binding site of receptor Peroxisome proliferator-activated receptor, PPAR-γ or PPARG (PDB 1FM9). Among the synthesized compounds, nine compounds were selected on the basis of docking score and evaluated for their in vivo anti-diabetic activity using Oral Glucose Tolerance Test (OGTT) in normal rats followed by Streptozotocin (STZ) - induced diabetes. Results indicated that compound M-14 (161.39 ±â€¯4.38) showed the highest reduction of blood glucose level comparable to that of the standard drug glibenclamide (140.29 ±â€¯1.24) in STZ model. Other compounds exhibited moderate to good anti hyperglycaemic activity. ADME studies was done using Molinspiration online software, revealed that all compounds (except M-11) are likely to be orally active as they obeyed Lipinski's rule of five.

Action and resistance mechanisms of antibiotics: A guide for clinicians.

Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and "bypass" of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.

Antibiotic susceptibility profile of Pseudomonas species isolated from clinical specimens to access, watch and reserve drugs across various hospital settings at a tertiary care hospital of central India.

Background and Objectives: Over the last decade, hospital-acquired infections, particularly in the critical care setting, have become more common, with Gram-negative bacterial infections having the highest prevalence. This study aims to determine the prevalence and antibiotic susceptibility pattern of Pseudomonas species to WHO's, aware class of antibiotics, which are commonly prescribed across various ICU's, medical and surgical wards of our tertiary care teaching hospital. Materials and Methods: This prospective study conducted from January 2021 to June 2022 at a tertiary care centre of central India identified Pseudomonas species from clinical samples using standard procedures and antimicrobial susceptibility testing performed as per Clinical Laboratory Standards Institute (CLSI) guidelines (M100; 32th Edition). Results: A total of 1490 non duplicate Pseudomonas species isolates were grown from 21,019 culture positive clinical samples, of which 1247 were Pseudomonas aeruginosa. Out of these 1247 Pseudomonas aeruginosa 384 were MDR (30.7%). Pseudomonas aeruginosa were most commonly isolated from the pus samples (85%). ICU isolates were significantly more resistant to antibiotics than those from other units. P. aeruginosa strains from ICUs showed the highest rates of resistance to ceftazidime (93.9%). Reserve drug colistin showed good susceptibility (98.2%). All the 18 colistin resistant strains were found to be negative for plasmid mediated mcr-1,2,3 genes. Conclusion: The study shall help to generate and disseminate the data so that proper antibiotic policy can be made for judicious use of Access, Watch and Reserve antibiotics and antibiotic de-escalation plan can be put forth.

A retrospective analysis on seroprevalence of acute viral hepatitis observed among dengue patients attending a tertiary care centre in central India.

PURPOSE: The present study was conducted retrospectively to assess the frequency of acute viral hepatitis among the clinically suspected dengue cases presented at our tertiary care centre during 2021. METHODS: To determine the presence of acute viral hepatitis; Hepatitis A virus (HAV) and Hepatitis E virus (HEV) infections, 104 specimens were selected from the dengue-suspected clinical specimens received during 2021 on the basis of acute viral hepatitis symptoms. Following this, serological diagnosis was performed on those samples using anti-HAV IgM and anti-HEV IgM ELISA kits. RESULTS: Based on sero-positivity for IgM antibodies, 3 (5.3%) dengue virus (DENV) seropositive samples were positive for both HAV and HEV, while among DENV seronegative cases, 11 (22.91%) samples were positive for HEV and 1 (2.08%) sample was positive for HAV, pointing towards misdiagnosis due to overlapping symptoms. Additionally, co-infection of HAV & HEV in 1 sample was also observed in this study. CONCLUSIONS: This study revealed the presence of acute hepatitis infections among the dengue cases during monsoon and post-monsoon season. Overlapping of the clinical manifestations of these diseases can create misdiagnosis incidences raising risk for underreporting of the true cases of acute viral hepatitis infection. Dengue-suspected patients with selected symptoms during the monsoon and post-monsoon season should additionally be screened for acute hepatitis infections, as suggested in this study.

Role and Responsibilities of Various Stakeholders in Pharmacovigilance (PV).

In this review paper, we have analyzed the potential and issues associated with Pharmacovigilance (PV). The analysis is divided into four sections: background, stakeholders, data sources, and medicinal chemistry. Each section discusses the current state, the future trends, and the best practices of Pharmacovigilance (PV). The main purpose, methods, results, and implications of our analysis are summarized. BACKGROUND: Pharmacovigilance (PV) is the science and practice of monitoring, evaluating, understanding, and preventing adverse drug reactions. Pharmacovigilance (PV) was established by the World Health Organization in response to the thalidomide tragedy of 1961. The main purpose of Pharmacovigilance (PV) is to ensure the safety and efficacy of drugs in clinical practice. Stakeholders: Pharmacovigilance (PV) involves various stakeholders, such as patients, pharmacists, pharmaceutical companies, healthcare professionals, and regulatory authorities. Each stakeholder has a different role and responsibility in reporting, processing, analyzing, and communicating information about adverse drug reactions. Patient engagement is a key factor for enhancing Pharmacovigilance (PV) practices. DATA SOURCES: Pharmacovigilance (PV) relies on data from various sources, such as clinical trials, spontaneous reports, electronic medical records, biomedical literature, and patient-reported data in online health forums. These data sources can provide valuable insights into the real-world use and safety of drugs, as well as the preferences and needs of patients. However, these data sources also pose challenges in terms of quality, validity, reliability, and accessibility. Medicinal Chemistry: Medicinal chemistry is the branch of chemistry that deals with the design, synthesis, and evaluation of new drugs and their biological effects. Medicinal chemistry can enhance Pharmacovigilance (PV) practices by finding new therapeutic indications for existing drugs or compounds that have already been tested for safety and efficacy. Medicinal chemistry also requires careful design and evaluation of covalent inhibitors, bi-substrate inhibitors, stabilizers of protein non-effective conformations, and hydrophobic pocket modifiers to ensure their safety and efficacy. IMPLICATIONS: Pharmacovigilance (PV) is a dynamic and evolving discipline that requires collaboration, regulation, education, and innovation to improve patient safety and care. This review aims to provide a comprehensive overview of the potential and issues associated with Pharmacovigilance (PV) practices.

Emergence of Multidrug-Resistant Non-Fermenting Gram-Negative Bacilli in a Tertiary Care Teaching Hospital of Central India: Is Colistin Resistance Still a Distant Threat?

Purpose Multidrug-resistant (MDR) organisms are being increasingly reported from India. This study aimed to determine the antibiotic susceptibility pattern of non-fermenting Gram-negative bacilli (NF-GNB) isolated from all the clinical samples to estimate the prevalence of MDR MDR NF-GNB and to screen for colistin-resistance genes among all colistin-resistant strains. Materials and methods This prospective study conducted from January 2021 to July 2022 at a tertiary care teaching hospital in central India identified MDR NF-GNB from clinical samples using standard procedures and antimicrobial susceptibility testing conducted as per Clinical Laboratory Standards Institute (CLSI) guidelines. Colistin-resistant strains identified by broth microdilution were further subjected to detection of plasmid-mediated colistin-resistant genes (mcr-1, mcr-2, mcr-3) by polymerase chain reaction (PCR). Results A total 2,106 NF-GNB were isolated from 21,019 culture positive clinical samples, of which 743 (35%) were MDR. Majority of MDR NF-GNB isolated were from pus (45.50%) followed by blood (20.50%). Out of 743 non-duplicate MDR non-fermenters,the most common were Pseudomonas aeruginosa (51.7%), Acinetobacter baumannii (23.4%),and others (24.9%).Around5.2% Pseudomonas aeruginosa and 2.3% Acinetobacter baumannii were resistant to colistin, and 88.2% were resistant to ceftazidime. Burkholderia cepacia complexwas 100% susceptible to minocycline and least susceptible to ceftazidime (28.6%). Out of 11, 10 (90.9%) Stenotrophomonas maltophilia were susceptible to colistin and least susceptible to ceftazidime and minocycline (27.3%). All 33 colistin-resistant strains (minimal inhibitory concentration ≥ 4 µg/mL) were found to be negative for mcr-1, mcr-2, and mcr-3 genes. Conclusion Our study showed a significantly wide variety of NF-GNB, ranging from Pseudomonas aeruginosa (51.7%), Acinetobacter baumannii (23.4%),to Acinetobacter haemolyticus (4.6%), Pseudomonas putida (0.9%), Elizabethkingia meningoseptica (0.7%), Pseudomonas luteola (0.5%), and Ralstonia pickettii (0.4%), which have not been commonly reported in literature. Of all the non-fermenters isolated in the present study, 35.28% were MDR, raising the concern for rationalizing antibiotic use and improving infection control measures to avert or slow the emergence of antibiotic resistance.

Intrauterine instillation of autologous platelet-rich plasma in infertile females with thin endometrium undergoing intrauterine insemination: an open-label randomized controlled trial.

BACKGROUND: Thin endometrium in infertile female patients has always been a clinical challenge for the treating reproductive physicians. OBJECTIVE: This study aimed to evaluate the effect of intrauterine instillation of autologous platelet-rich plasma on endometrial thickness and vascularity in infertile female patients with thin endometrium undergoing ovarian stimulation with intrauterine insemination. STUDY DESIGN: This prospective randomized control study included 120 women undergoing ovarian stimulation with intrauterine insemination, aged between 21 and 37 years, with persistent thin endometrium (<7 mm) on ≥1 cycle in previous ovarian stimulation cycles, even after conventional treatment with estradiol valerate. The women were randomly assigned to study group A and control group B. Baseline endometrial thickness and endometrial vascularity were noted. Intrauterine instillation of autologous platelet-rich plasma was done on the day of trigger in group A, whereas estradiol valerate was given in group B. Another evaluation of endometrial parameters was done on the day of intrauterine insemination. The cycle was repeated for 3 cycles or until the pregnancy was achieved, whichever occurred earlier. Parameters were noted for both groups. Primary outcomes were the change in endometrial thickness and endometrial vascularity. Secondary outcomes were positive pregnancy rate and clinical pregnancy rate. RESULTS: In group A, mean pre-platelet-rich plasma endometrial thickness was 4.66±0.79 mm, which significantly increased to 7.47±0.85 mm after platelet-rich plasma instillation (P<.05) after 3 cycles. This increase was significantly greater than that observed in group B. There was significant increase in endometrial vascularity in group A compared with group B (P<.05). The positive pregnancy rate and clinical pregnancy rate in group A were 23.73% and 18.64%, respectively, and significantly higher than those in group B. CONCLUSION: Autologous platelet-rich plasma is a promising, easily procurable, and novel option for management of infertile females with thin endometrium not responding to conventional treatment. Using it in intrauterine insemination cycles can reduce costs and psychological burden of this subgroup of women by reducing the need for resorting to advanced options such as in vitro fertilization and surrogacy.

Continued dominance of dengue virus serotype 2 during the recent Central India outbreaks (2019-2021) with evidence of genetic divergence.

Central India faced major dengue outbreaks in 2019 and 2021. In the present study, we aimed to identify the dengue virus serotypes and genotypes circulating in Central India during the COVID pre-pandemic year (2019) and ongoing-pandemic year (2021). For this purpose, the suspected cases were first tested by serological assays. Sero-positive samples were then subjected to molecular diagnosis by RT-PCR and semi-nested PCR. The serotypes obtained were confirmed by nucleotide sequencing. A phylogenetic analysis of serotypes was performed to identify the circulating genotypes. All four DENV serotypes were detected during 2019 and 2021, with the predominance of DENV2. Cases with multiple DENV serotype infections were also identified, involving DENV-2 in all the coinfections. Genotyping revealed that DENV-1 (Genotype V, American/African), DENV-2 (Genotype IV, Cosmopolitan), DENV-3 (Genotype III, Cosmopolitan), and DENV-4 (Genotype I) were involved during both outbreaks. DENV-2 detected in 2019 and 2021 has diverged from the previous strains detected in Central India (2016 and 2018), which may account for the higher transmission of DENV-2 during these outbreaks. The detection of heterologous DENV serotypes with high transmission efficiency calls for continuous viral monitoring and surveillance, which will contribute to a better understanding of changing viral dynamics and transmission patterns.

Functional and Tableting Properties of Alkali-Isolated and Phosphorylated Barnyard Millet (Echinochloa esculenta) Starch.

The functional and tableting properties of barnyard millet starch (Echinochloa esculenta) were investigated in its native (alkali-treated) and chemically modified (phosphorylated) states. The grains were pulverized, soaked, and ground before filtration to separate starch and protein. Multiple NaOH treatments were performed. The starch was washed, neutralized, and dried. Sodium tripolyphosphate (STPP) and sodium sulfate were used to modify the starch, followed by maceration, washing, and drying to remove unreacted chemicals. The amylose content of alkali-treated barnyard millet starch increased by 19.96 ± 3.56% w/w. The amount of protein, the kind of starch used, and the size of the starch granules, all affected the ability of the starch granules to swell up. It was observed that alkali-extracted barnyard millet starch (AZS) has a swelling power of 194.3 ± 0.0064% w/w. The swelling capacity of treated starch was lesser as compared to the native alkali barnyard millet starch. Decrement in swelling power of phosphorylated starch was observed due to tightening of bonds in the molecular structure. The moisture content of the excipients may affect the overall stability of the formulation. The moisture content of the AZS was found to be 15.336 ± 1.012% w/w. Compared to AZS, cross-linked barnyard millet starch had a moisture content that was up to 20% lower than AZS. The Hausner ratio for phosphorylated starch was found to be 1.25, which indicates marked flow property. Similar morphologies could be seen in the alkali-isolated barnyard millet starch and the cross-linked/phosphorylated barnyard millet that was cross-linked using a mixture of sodium sulfate and sodium tripolyphosphate. The modest degree of substitution would have no effect on the surface morphology as shown by the scanning electron microscopic study. The crushing and compacting abilities of modified barnyard millet starch were also improved, but its friability and rate of disintegration were decreased. The whole study revealed that after cross-linking, barnyard millet had good tableting properties and it can be used as an excipient in drug delivery.

Performance Evaluation of Different RT-PCR Kits for the Direct Detection of SARS-CoV-2 in Preheated Specimens.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created high demand for molecular kits and consumables for mass screening of suspected individuals. Direct real-time polymerase chain reaction (RT-PCR) assay without nucleic acid extraction has several advantages in saving testing time and cost and helps in the rapid reporting of SARS-CoV-2. The present study evaluated the analytical performance of four SARS-CoV-2 RT-PCR for direct RT-PCR testing using preheated specimens. Methods A total of 100 clinical specimens were selected and divided into three different groups: (1) group I: 20 SARS-CoV-2 positive specimens with high viral load, viz., low Ct values (< 30 Ct), (2) group II: 50 SARS-CoV-2 positive specimens with low viral load, viz., high Ct values (> 30 Ct), and (3) group III: 30 SARS-CoV-2 negative specimens. Specimens were heat-inactivated at 70°C for 10 minutes and cooled down at 4°C and were evaluated for standard and direct RT-PCR method by using ViralDtect-II Multiplex Real-Time PCR kit, TaqPath COVID-19 Combo kit, COVIDsure Pro Multiplex RT-PCR kit, and Hi-PCR Coronavirus (COVID-19) Multiplex Probe PCR kit. Results Results showed that except ViralDtect-II kit, the other three TaqPath COVID-19 Combo kit, COVIDsure Pro kit, and Hi-PCR Coronavirus (COVID-19) RT-PCR kit were able to amplify all the SARS-CoV-2 genes in the direct RT-PCR method using preheated specimens. In group I specimens, 100% sensitivity was observed in all three RT-PCR kits. In group II specimens, COVIDsure Pro kit was found to be superior among other kits. Conclusion Direct RT-PCR method during pandemic situation is valuable and cost effective for the detection of SARS-CoV-2. All three TaqPath COVID-19 Combo kit, COVIDsure Pro kit, and Hi-PCR Coronavirus (COVID-19) RT-PCR kit can be used for direct RT-PCR method and COVIDsure Pro kit performance was found to be superior among all.

Exploring the Multitarget Potential of Iridoids: Advances and Applications.

Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentan[c]-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases.

2-Substituted-3-(5-Substituted-1,3,4-oxadiazol/thiadiazol-2-yl) Thiazolidin-4-one Derivatives: Synthesis, Anticancer, Antimicrobial, and Antioxidant Potential.

In this innovative research, a novel series of thiazolidin-4-one analogues having a 1,3,4-oxadiazole/thiadiazole moiety were derived and the structures of all the newly obtained molecules were established using different physicochemical and analytical means (1H-NMR, FTIR, mass spectra, and elemental analyses). The synthesized molecules were then investigated for their antiproliferative, antimicrobial, and antioxidant potential. The cytotoxicity screening studies revealed that analogues D-1, D-6, D-15, and D-16 possessed comparable efficacy, within the IC50 range (1 to 7 µM), when taking doxorubicin as a reference drug (IC50 = 0.5 µM). The antimicrobial activity was assessed using different Gram-(+) and Gram-(-) bacterial and fungal strains and the results revealed that molecules D-2, D-4, D-6, D-19, and D-20 possessed potent activity against selective strains of microbes with MIC ranges of 3.58 to 8.74 µM. The antioxidant evaluation was performed using the DPPH assay and the screening results revealed that analogue D-16 was the most potent derivative (IC50 = 22.3 µM) when compared with the positive control, ascorbic acid (IC50 = 111.6 µM). Structure-activity relationship (SAR) studies of the synthesized novel derivatives revealed that para-substituted halogen and hydroxy derivatives have remarkable potential against the MCF-7 cancer cell line and antioxidant potential. Similarly, electron-withdrawing groups (Cl/NO2) and -donating groups at the para position possess moderate to promising antimicrobial potential.

Current Developments in the Pyran-Based Analogues as Anticancer Agents.

Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.'Pyran' is one of the most significant non-aromatic, sixmembered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in vitro (cell based testing), in vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review.

Advances in Synthesis, Derivatization and Bioactivity of Isatin: A Review.

BACKGROUND: Isatin (IST) is a crucial pharmacologically active compound, chemically known as indole- 1H-2,3-dione. Development of different IST based analogues acquired significant awareness because of its pronounced therapeutic importance such as analgesic, anticancer, anti-inflammatory, antitubercular, antimicrobial, antifungal, antiviral (effective against SARS coronavirus 3C protease) and many other activities, and represents an important class of heterocyclic compounds that can be used as a precursor for the synthesis of many useful drugs. OBJECTIVE: Previously, many articles were reported on IST synthesis and its different pharmacological activities but herein, we mentioned 59 different synthesis schemes of several IST derivatives/hybrids derived from the substitution of the nitrogen, aromatic ring, the second and third position of IST along with most potent molecule among each of synthesized libraries with their structural activity relationship (SAR). Using these standardized approaches, several biologically important compounds were developed like sunitinib, nintedanib, indirubin, etc and several studies have been carried out nowadays to develop newer compounds having fewer side effects and also overcome the problem of resistance. CONCLUSION: This report critically reviews the different strategies for the designs and synthesis of several IST based compounds having different biological activities with SAR, which can favour further investigation and modification for the development of new and more potent entities.

A pandemic recap: lessons we have learned.

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.