Oral carcinogenesis and non-invasive biomarkers for the diagnosis of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most prevalent cancer in Pakistani population because of consumption of different tobacco-containing products whether smoked or chewed. These patients commonly report at a late stage of the disease. The patient's survival only depends upon early-stage diagnosis. Literature has reported that there is an increased tendency of transformation of oral potentially malignant disorder (OPMD) into OSCC. Biopsy is the gold standard measure for diagnosis but for OPMD cases biopsy was not recommended and most of the times the patients were also not willing to have a biopsy done. So, along with the biopsy there is a need for non-invasive protein biomarker that might aid in the early detection of oral cancer as well as highlight the high-risk individuals. This short communication focuses on the role of early diagnostic biomarkers present in literature, such as synuclein-γ (SNCG), Squamous cell carcinoma antigen (SCCAg), p53, MMPs-12, and IL-6. Furthermore, application of these biomarkers in multi-centre longitudinal studies is needed to establish their role as a non-invasive diagnostic biomarker for OSCC.

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review.

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007-2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau-Demjanov rearrangement, Aza-Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.

Simmons-Smith Cyclopropanation: A Multifaceted Synthetic Protocol toward the Synthesis of Natural Products and Drugs: A Review.

Simmons-Smith cyclopropanation is a widely used reaction in organic synthesis for stereospecific conversion of alkenes into cyclopropane. The utility of this reaction can be realized by the fact that the cyclopropane motif is a privileged synthetic intermediate and a core structural unit of many biologically active natural compounds such as terpenoids, alkaloids, nucleosides, amino acids, fatty acids, polyketides and drugs. The modified form of Simmons-Smith cyclopropanation involves the employment of Et2Zn and CH2I2 (Furukawa reagent) toward the total synthesis of a variety of structurally complex natural products that possess broad range of biological activities including anticancer, antimicrobial and antiviral activities. This review aims to provide an intriguing glimpse of the Furukawa-modified Simmons-Smith cyclopropanation, within the year range of 2005 to 2022.

Antileishmanial Activities of (Z)-2-(Nitroimidazolylmethylene)-3(2H)-Benzofuranones: Synthesis, In Vitro Assessment, and Bioactivation by NTR 1 and 2.

The antileishmanial activity of a series of (Z)-2-(heteroarylmethylene)-3(2H)-benzofuranone derivatives, possessing 5-nitroimidazole or 4-nitroimidazole moieties, was investigated against Leishmania major promastigotes and some analogues exhibited prominent activities. Compounds with IC50 values lower than 20 µM were further examined against L. donovani axenic amastigotes. Evaluated analogues in 5-nitroimidazole subgroup demonstrated significantly superior activity (~17-88-folds) against L. donovani in comparison to L. major. (Z)-7-Methoxy-2-(1-methyl-5-nitroimidazole-2-ylmethylene)-3(2H)-benzofuranone (5n) showed the highest L. donovani anti-axenic amastigote activity with IC50 of 0.016 µM. The cytotoxicity of these analogues was determined using PMM peritoneal mouse macrophage and THP-1 human leukemia monocytic cell lines and high selectivity indices of 26 to 431 were obtained for their anti-axenic amastigote effect over the cytotoxicity on PMM cells. Further studies on their mode of action showed that 5-nitroimidazole compounds were bioactivated predominantly by nitroreductase 1 (NTR1) and 4-nitroimidazole analogues by both NTR1 and 2. It is likely that this bioactivation results in the production of nitroso and hydroxylamine metabolites that are cytotoxic for the Leishmania parasite.

Cross-coupling reactions towards the synthesis of natural products.

Cross-coupling reactions are powerful synthetic tools for the formation of remarkable building blocks of many naturally occurring molecules, polymers and biologically active compounds. These reactions have brought potent transformations in chemical and pharmaceutical disciplines. In this review, we have focused on the use of cross-coupling reactions such as Suzuki, Negishi, Heck, Sonogashira and Stille in the total synthesis of some natural products of recent years (2016-2020). A short introduction of mentioned cross-coupling reactions along with highlighted aspects of natural products has been stated in separate sections. Additionally, few examples of natural products via incorporation of more than one type of cross-coupling reaction have also been added to demonstrate the importance of these reactions in organic synthesis.

Nanobioremediation: A sustainable approach towards the degradation of sodium dodecyl sulfate in the environment and simulated conditions.

Nanotechnology has gained huge importance in the field of environmental clean-up today. Due to their remarkable and unique properties, it has shown potential application for the remediation of several pesticides and textile dyes. Recently it has shown positive results for the remediation of sodium dodecyl sulfate (SDS). One of the highly exploited surfactants in detergent preparation is anionic surfactants. The SDS selected for the present study is an example of anionic linear alkyl sulfate. It is utilized extensively in industrial washing, which results in the high effluent level of this contaminant and ubiquitously toxic to the environment. The present review is based on the research depicting the adverse effects of SDS in general and possible strategies to minimizing its effects by bacterial degradation which are capable of exploiting the SDS as an only source of carbon. Moreover, it has also highlighted that how nanotechnology can play a role in the remediation of such recalcitrant pesticides.

Ultrasound Assisted Synthesis and In Silico Modelling of 1,2,4-Triazole Coupled Acetamide Derivatives of 2-(4-Isobutyl phenyl)propanoic acid as Potential Anticancer Agents.

The development of an economical method for the synthesis of biologically active compounds was the major goal of this research. In the present study, we have reported the ultrasound-radiation-assisted synthesis of a series of novel N-substituted 1,2,4-triazole-2-thiol derivatives. The target compounds 6a−f were efficiently synthesized in significant yields (75−89%) by coupling 1,2,4-triazole of 2-(4-isobutylphenyl) propanoic acid 1 with different electrophiles using ultrasound radiation under different temperatures. The sonication process accelerated the rate of the reaction as well as yielded all derivatives compared to conventional methods. All derivatives were confirmed by spectroscopic (FTIR, 1HNMR, 13CNMR, HRMS) and physiochemical methods. All derivatives were further screened for their anticancer effects against the HepG2 cell line. Compound 6d containing two electron-donating methyl moieties demonstrated the most significant anti-proliferative activity with an IC50 value of 13.004 µg/mL, while compound 6e showed the lowest potency with an IC50 value of 28.399 µg/mL. The order of anticancer activity was found to be: 6d > 6b > 6f > 6a > 6c > 6e, respectively. The in silico modelling of all derivatives was performed against five different protein targets and the results were consistent with the biological activities. Ligand 6d showed the best binding affinity with the Protein Kinase B (Akt) pocket with the lowest ∆G value of −176.152 kcal/mol. Compound 6d has been identified as a promising candidate for treatment of liver cancer.

In-vitro cytotoxic evaluation, hemolytic and thrombolytic potential of newly designed acefylline based hydrazones as potent anticancer agents against human lung cancer cell line (A549).

Hydrazones of theophylline-7-acetic acid 5a-g have been synthesized using ultrasonic irradiation as well as conventional heating system and analyzed for their anticancer characteristics against human lung cancer cell line (A549). Compound 5g with cell viability 33.19±0.49% (100 µg/µL) compared to the starting reference drug acefylline having cell viability 86.32±11.75% (100 µg/µL) was found to be the most active anticancer agent among all. The synthesized derivatives were also exposed to hemolytic and thrombolytic studies to determine their cytotoxic profile and results revealed their low toxicity and moderate clot lysis activity.

In-vitro cytotoxic evaluation of newly designed ciprofloxacin-oxadiazole hybrids against human liver tumor cell line (Huh7).

Fluoroquinolones are targets of interest due to their broad spectrum antibacterial activity. Structure-activity relationship (SAR) of fluoroquinolones clearly indicates that substitution at C-7 position enhances the lipophilicity of these scaffolds resultantly affording pharmacologically significant compounds. Therefore, various ciprofloxacin-oxadiazole hybrids were synthesized and characterized by spectral analysis. Cytotoxic activity of these derivatives was assessed using human liver tumor cells (Huh7). One dose anticancer test results revealed moderate cytotoxicity of the newly synthesized compounds against this cell line. As the only compound 4a depicted comparatively lower cell viability value (81.91% using 100µg/mL concentration) than the other compounds.

In-silico modeling and in-vitro studies of 2,1-benzothiazine-2,2-dioxide based hydrazone derivatives as α-glucosidase inhibitors.

Diabetes mellitus (DM) is a metabolic disorder characterized by frequent urination, hunger and high blood sugar level. α-glucosidase inhibitors are considered as a frontline treatment for the DM. This research article deals with the identification of benzothiazine derivatives as α-glucosidase inhibitors through in-silico techniques and then the confirmation through in-vitro analysis. Molecular docking studies were carried out to find out the binding interactions of targeted molecules with receptor molecule i.e., α-glucosidase enzyme. The synthetic compounds 1 (a-n), 2 (a-d) and 3 (a-b) were evaluated for in-vitro alpha glucosidase inhibitory activities that resulted in the discovery of various potent molecules. Majority of the compounds (1c, 1f, 1g, 1k-n, 2a-d and 3a-b) exhibited good inhibitory activity against α-glucosidase. Compounds 1c, 1g, 1k and 1m appeared as the potent active compounds with the IC50 values 17.44, 27.64, 24.43, 42.59 and 16.90 µM respectively. Compounds 1c & 2c were found almost 3-folds more active than the standard acarbose. The study may lead to discover potent drug candidates with less complication for the treatment of the type II diabetes mellitus.

Facile green approach towards the synthesis of some phenyl piperazine based dithiocarbamates as potent hemolytic and thrombolytic agents.

The facile and efficient protocol for the synthesis of N-phenyl piperazine based di-thio-carbamates has been reported under neat conditions. A library of novel piperazine based di-thio-carbamates (3a-h) in excellent yields has been prepared. Solvent free, catalyst free and easy work up conditions make this protocol an attractive synthetic protocol to achieve novel biologically active di-thio-carbamates. The synthesized molecules have been characterized by FT-IR, 1HNMR and 13CNMR spectroscopic techniques. The pharmacological aspects of these derivatives have been evaluated via hemolysis and thrombolysis. All the target molecules (3a-h) exhibit mild to medium potential as hemolytic and thrombolytic agents. Among the synthesized derivatives, compound 3c showed least cytotoxicity and better thrombolytic potential.

Synthesis, spectral analysis and biological evaluation of 2-{[(morpholin-4-yl)ethyl]thio}-5-phenyl/aryl-1,3,4-oxadiazole derivatives.

A series of new derivatives of 4-(2-chloroethyl)morpholine hydrochloride (5) were efficiently synthesized. Briefly, different aromatic organic acids (1a-f) were refluxed to acquire respective esters (2a-f) using conc. H2SO4 as catalyst. The esters were subjected to nucleophillic substitution by monohydrated hydrazine to acquire hydrazides (3a-f). The hydrazides were cyclized with CS2 in the presence of KOH to yield corresponding oxadiazoles (4a-f). Finally, the derivatives, 6a-f, were prepared by reacting oxadiazoles (4a-f) with 5 using NaH as activator. Structures of all the derivatives were elucidated through 1D-NMR EI-MS and IR spectral data. All these molecules were subjected to antibacterial and hemolytic activities and showed good antibacterial and hemolytic potential relative to the reference standards.

Awareness and current knowledge of epilepsy.

Epilepsy is a severe neural disorder that affects approximately fifty million individuals globally. Despite the fact that for most of the people with epilepsy, convulsions are better controlled by current accessible antiepileptic medicines, yet there are more than 30% of individuals affected with medically intractable epilepsy and around 30-40% of all patients with epilepsy affected by many adverse reactions and convulsion resistance to the present antiepileptic drugs. Consequently, various scientists attempt to develop new strategies to treat epilepsy, for instance, to find out novel antiepileptic ingredients from traditional medicines. This work aims to present a complete summary of natural medicines prescribed as antiepileptic agents all over the world by ethnic groups and different tribes. We undertook an extensive bibliographic analysis by searching peer reviewed papers and classical textbooks and further consulting well accepted worldwide scientific databases. We carried out PubMed, EMbase and CENTRAL searches by means of terms such as "antiepileptic" and "anti-convulsant" activity of plants. Medicinal plants have been prescribed to treat epilepsy and have been recognized as antiepileptic medicines. In this review, a variety of herbs have been reviewed for thorough studies such as Cuminum cyminum, Butea monosperma, Solanum americanum, Anacyclus pyrethrum, Leonotis leonurus, Elaeocarpus ganitrus and Angelica archangelica. This paper shows that it was high time experimental studies are increased to obtain novel potential active principles from medicinal plants. Plant extracts and their chemical constituents should be further evaluated to clarify their mechanisms of action. This paper provides a solid base upon which to further investigate the clinical efficacy of medicinal plants that are both currently prescribed by physicians as traditional antiepileptic agents, but also could be effective as an antiepileptic drug with further research and study.

Synthesis, characterization, antibacterial, hemolytic and thrombolytic activity evaluation of 5-(3-chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives.

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.

M-SAKHI-Mobile health solutions to help community providers promote maternal and infant nutrition and health using a community-based cluster randomized controlled trial in rural India: A study protocol.

Reduction of childhood stunting is difficult to achieve by interventions that focus only on improving nutrition during infancy. Comprehensive interventions that extend through the continuum of care from pregnancy to infancy are needed. Mobile phones are now successfully being used for behaviour change communication to improve health. We present the methodology of an mHealth intervention "Mobile Solutions Aiding Knowledge for Health Improvement" (M-SAKHI) to be delivered by rural community health workers or Accredited Social Health Activists (ASHAs) for rural women, below or up to 20 weeks of pregnancy through delivery until their infant is 12 months of age. This protocol paper describes the cluster randomized controlled trial to evaluate the effectiveness of M-SAKHI. The primary objective of the trial is to reduce the prevalence of stunting (height-for-age < -2 z-score) in children at 18 months of age by 8% in the intervention as compared with control. The secondary objectives include evaluating the impact on maternal dietary diversity, birth weight, infant and young child feeding practices, infant development, and child morbidity, along with a range of intermediate outcomes for maternal, neonatal, and infant health. A total of 297 ASHAs, five trained counsellors, and 2,501 participants from 244 villages are participating in this study. The outcome data are being collected by 51 field research officers. This study will provide evidence regarding the efficacy of M-SAKHI to reduce stunting in young children in rural India, and if effective, the cost-effectiveness of M-SAKHI.

Workplace violence against resident doctors: A multicentric study from government medical colleges of Uttar Pradesh.

According to the World Health Organization, between 8% and 38% of health workers suffer physical violence at some point in their careers. This multicentric study was conducted to find the prevalence, perceived risk factors, and measures to prevent workplace violence among doctors. The sample consisted of all 2nd- and 3rd-year resident doctors (n = 305) from three colleges in Uttar Pradesh. An anonymous, pretested in a similar setting, self-administered questionnaire was used. 69.5% of doctors reported to have experienced violence in one or other form in the past 1 year. In most incidents, relatives and attendants (69.3%) were involved in violence. No action was taken immediately in regard to violence in 35.3% of instances; 60.3% of study participants reported that they had repeated disturbing memories, thoughts, or images of the attack. Nonavailability of medicines (38.6%) and less staff (36.7%) were cited as top reasons behind violence.

A new approach to design 3(3-sulfamoylbenzamido) benzoic acid containing transition metal complexes: Characterization and Biological activities.

Zn, Cu, Co and Ni are biocompatible metals as they are active center of many enzymes in the human body. Incorporation of these biocompatible metals into 3-(o-Sulfamoylphenyl) carbamoylbenzoic acid (I) makes them able to prove an excellent antimicrobial agent. In the present study Ni (II), Co (II), Cu(II) and Zn (II) complexes (III-VI) were synthesized from ligand (I) derive from 3-(o-Sulfamoylphenyl) carbamoylbenzoic acid and zinc, nickel, cobalt acetate tetrahydrate/copper acetate monohydrate. Synthesized complexes (III-VI) were characterized by FT-IR, 1H NMR and 13CNMR. III-VI have 81-93% yield while melting points recorded were in the range of 209-239oC. Purity of ligands and their respective complexes was confirmed by TLC. Results of antibacterial properties suggested that III, IV, V and VI were highly active against gram +ve (S. epidermidis, B. subtilis. S. aureus, S. mutans) and gram -ve bacteria (E. coli and P. aruginosa). Comparison was also performed to check whether metal complexes or ligand with its derivative exhibit best result against all tested strains. The anthelmintic activity of the complexes III-VI against tape worm, liver fluke, thread worm, and hook worm using three different concentrations (15, 30, 45mg/mL), significantly (p<0.01) paralyzed the worms followed by death, which was comparable with that of the standard. Overall results indicated that S. epidermidis, S. mutans, E. coli and B. subtilis are very sensitive to complex III & IV and can be used for treatment of bacterial infections whereas Complex-V, could a potent target for anti-parasite therapy.

Prevalence and co-infection of Malaria and Typhoid in the local population of Faisalabad, Pakistan.

Malaria and typhoid fever are among the major infectious diseases which impose significant health and socioeconomic burden on affected populations. Further, co-infection and resembling symptomatology in both infections, mostly leads to misdiagnosis and mistreatment. So co-infection of malaria and typhoid fever is becoming a major issue in tropical and subtropical countries. The current study was planned to explore the rate of co-infection of malaria and typhoid fever to show the diagnostic challenges and people health implications in the local population of Faisalabad-Pakistan. For this purpose, 144 samples (n=144) were collected from suspected subjects both male (n=74) and female (n=70) (comprises of three age group ranges viz >01-10, 11-20 and above 20 years old) of typhoid fever and malaria from October to December 2017 at Children Hospital, Faisalabad-Pakistan. Thick smear as a gold standard technique for malaria diagnosis and Widal agglutination technique for typhoid diagnosis were used. Results revealed that the prevalence of co-infection in selected subjects was 6.3% (n=9) with higher prevalence in female subjects (7.1%) as compared to males (5.4%). Further, it was also reported that age groups >01-10 years old, 11-20 years old and 21-above years old have6.6 % (n=75), 5.7 % (n=35) and 5.8% (n=34), coinfection prevalence respectively. In the present study, it could be concluded that although the prevalence of co-infection of malaria and typhoid fever in the studied population was possible but sensitivity of diagnostic tools was limited, so more reliable, specific and sensitive diagnostic tools are required to report confidently more precise correlation of these infectious diseases.

Effectiveness of weekly cell phone counselling calls and daily text messages to improve breastfeeding indicators.

BACKGROUND: Every year, nearly one million deaths occur due to suboptimal breastfeeding. If universally practiced, exclusive breastfeeding alone prevents 11.6% of all under 5 deaths. Among strategies to improve exclusive breastfeeding rates, counselling by peers or health workers, has proven to be highly successful. With growing availability of cell phones in India, they are fast becoming a medium to spread information for promoting healthcare among pregnant women and their families. This study was conducted to assess effectiveness of cell phones for personalized lactation consultation to improve breastfeeding practices. METHODS: This was a two arm, pilot study in four urban maternity hospitals, retrained in Baby Friendly Hospital Initiative. The enrolled mother-infant pairs resided in slums and received healthcare services at the study sites. The control received routine healthcare services, whereas, the intervention received weekly cell phone counselling and daily text messages, in addition to counselling the routine healthcare services. RESULTS: 1036 pregnant women were enrolled (518 - intervention and 518 - control). Rates of timely initiation of breastfeeding were significantly higher in intervention as compared to control (37% v/s 24%, p < 0.001). Pre-lacteal feeding rates were similar and low in both groups (intervention: 19%, control: 18%, p = 0.68). Rate of exclusive breastfeeding was similar between groups at 24 h after delivery, but significantly higher in the intervention at all subsequent visits (control vs. intervention: 24 h: 74% vs 74%, p = 1.0; 6 wk.: 81% vs 97%, 10 wk.: 78% vs 98%, 14 wk.: 71% vs 96%, 6 mo: 49% vs 97%, p < 0.001 for the last 4 visits). Adjusting for covariates, women in intervention were more likely to exclusively breastfeed than those in the control (AOR [95% CI]: 6.3 [4.9-8.0]). CONCLUSION: Using cell phones to provide pre and postnatal breastfeeding counselling to women can substantially augment optimal practices. High rates of exclusive breastfeeding at 6 months were achieved by sustained contact and support using cell phones. This intervention shows immense potential for scale up by incorporation in both, public and private health systems. TRIAL REGISTRATION: This study was retrospectively registered with Clinical Trial Registry of India ( http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=3060 ) Trial Number: CTRI/2011/06/001822 on date 20/06/2011.

Synthesis, spectral analysis and antibacterial activity of some novel 5-substituted-2-((6-bromo-3,4-methylenedioxybenzyl)thio)-1,3,4-oxadiazole derivatives.

A number of novel 5-substituted-2-((6-bromo-3,4-methylenedioxybenzyl)thio)-1,3,4-Oxadiazole derivatives (6a-l) have been synthesized to evaluate their antibacterial activity. Using aryl/aralkyl carboxylic acids (1a-l) as precursors, 5-substituted-1,3,4-Oxadiazol-2-thiols (4a-l) were yielded in good amounts. The derivatives, 4a-l, were subjected to electrophilic substitution reaction on stirring with 6-bromo-3,4-methylenedioxybenzyl chloride (5) in DMF to synthesize the required compounds. All the synthesized molecules were well characterized by IR, 1H-NMR, 13C-NMR and EIMS spectral data and evaluated for antibacterial activity against some bacterial strains of Gram-bacteria. The molecule, 6d, demonstrated the best activity among all the synthesized molecules exhibiting weak to moderate inhibition potential.