Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review.

An unprecedented global health crisis has developed due to the emergence of the mysterious coronavirus-2 of the severe acute respiratory syndrome, which has resulted in millions of deaths around the globe, as no therapy could control the 'cytokine storm'. Consequently, many vaccines have been developed and several others are being developed for this infection. Although most of the approved vaccines have been highly effective, many developing, and economically poor countries are still deprived of vaccination against SARS-CoV-2 due to the unequal distribution of vaccines worldwide. Furthermore, the uncertainty about the effectiveness of the available vaccines against the emerging mutants and variants also remains a matter of concern. Due to the multistep pathogenesis and unique features, combination therapy using safe immunomodulatory and antiviral drugs should be considered as the most effective and acceptable therapeutic regimen for this infection. Based on a thorough assessment of the literature, it was determined that it would be interesting to study the therapeutic potential of ivermectin and doxycycline, given their roles in several biological pathways involved in SARS CoV-2 pathogenesis. Following that, a comprehensive literature search was undertaken using Scopus, Web of Science, and Pubmed, depending on the inclusion and exclusion criteria. The present study provides a mechanism and comprehensive report, highlighting the role of combined therapy with ivermectin and doxycycline in alleviating the 'cytokine storm' of COVID-19 infection.

Antitumor and hepatoprotective effect of Cuscuta reflexa Roxb. in a murine model of colon cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta reflexa Roxb. (C. reflexa) is a well-known traditional herbal plant, with numerous inherent therapeutic potentials including anticancer, antitumor, antibacterial, analgesic, anthelmintic, laxative and others. Moreover, the anticancer and antitumor potentials of this herb are ongoing with several trails, thus an attempt was made to assess the anticancer and hepatoprotective potentials of traditional C. reflexa herbs. METHOD: The dried ethanolic extract of C. reflexa was tested for acute oral toxicity in the treated animals subsequently their behavioral, neurological, and autonomic profiles changes were observed. The preliminary anti-cancer effects of extracts against 1, 2- Dimethyl hydrazine (DMH) induced animals were assessed through barium enema X-ray, colonoscopy, and Aberrant crypt foci (ACF) studies. The blood samples of the animals (treated and untreated) were collected and their in-vitro histological parameters were evaluated by the experienced technician. RESULTS: It was observed that C. reflexa significantly reduced Disease activity indexing (DAI) level and ACF counting, as well as demonstrated similar activity as of the standard drug 5-Fluorouracil (5-FU). Histopathological results revealed that the apoptotic bodies decreased in the DMH-induced group (group II) during cancer progression while in 5-FU treated (group III) and C. reflexa treated (group IV and V) animals the apoptotic bodies were increased. Inversely, the mitotic bodies increased in group II animals and reduced in group III, IV, and V animals. In the colonic section, DMH-induced cancer assay exhibited significant effects on the levels of hemoglobin, Packed cell volume (PCV), Red blood cell (RBC) counts, Mean corpuscular hemoglobin concentration (MCHC), Mean corpuscular volume (MCV), and Mean cell hemoglobin (MCH), and was found to be less in group II animals whereas administration of C. reflexa efficiently recovered back the loss probably by healing the colon damage/depletion of cancer progression. Moreover, compared to the group II animals, the neutrophil count was within the normal range in C. reflexa administered group. CONCLUSIONS: In the present study, the major hematological parameters significantly increased within DMH treated animals and exhibited extensive damage in the hepatic regions. Moreover, the histopathological findings demonstrated that the C. reflexa extracts potentially reduced the cell proliferation, with no toxicity. The C. reflexa extracts exhibited impending anti-cancer activity as well as protected the hepatic cells and thus could be potentially used in the management of colon or colorectal cancer and hepatic impairments.

Novel quinazoline-based EGFR kinase inhibitors: A review focussing on SAR and molecular docking studies (2015-2019).

The over expression of EGFR has been recognized as the driver mechanism in the occurrence and progression of carcinomas such as lung cancer, breast cancer, pancreatic cancer, etcetera. EGFR receptor was thus established as an important target for the management of solid tumors. The occurrence of resistance caused as a result of mutations in EGFR has presented a formidable challenge in the discovery of novel inhibitors of EGFR. This has resulted in the development of three generations of EGFR TKIs. Newer mutations like C797S cause failure of Osimertinib and other EGFR TKIs belonging to the third-generation caused by the development of resistance. In this review, we have summarized the work done in the last five years to overcome the limitations of currently marketed drugs, giving structural activity relationships of quinazoline-based lead compounds synthesized and tested recently. We have also highlighted the shortcomings of the currently used approaches and have provided guidance for circumventing these limitations. Our review would help medicinal chemists streamline and guide their efforts towards developing novel quinazoline-based EGFR inhibitors.

Recent advancement in the discovery and development of anti-epileptic biomolecules: An insight into structure activity relationship and Docking.

Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy. The drug development has shown a hope to medicinal chemists and researchers to carry further research by going through a substantial literature survey. This review article attempts to describe the recent developments in the anti-epileptic agents, pertaining to different molecular scaffolds considering their structure-activity relationship, docking studies and their mechanism of actions.

Current status of pyrazole and its biological activities.

Pyrazole are potent medicinal scaffolds and exhibit a full spectrum of biological activities. This review throws light on the detailed synthetic approaches which have been applied for the synthesis of pyrazole. This has been followed by an in depth analysis of the pyrazole with respect to their medical significance. This follow-up may help the medicinal chemists to generate new leads possessing pyrazole nucleus with high efficacy.

Design, synthesis, and in-vivo pharmacological screening of N,3-(substituted diphenyl)-5-phenyl-1H-pyrazoline-1-carbothioamide derivatives.

Various 3,5-(substituted diphenyl)-4,5-dihydro-pyrazole-1-carbothioic acid phenylamides were synthesized starting from substituted acetophenones. Structures of the compounds were confirmed on the basis of spectral data. The compounds were evaluated for their anticonvulsant and antidepressant activity. Interestingly, out of 26 compounds, four (3f, 3g, 3t, and 3u) were found to protect 100% of the animals in the MES screen at a dose of 25 mg/kg. They were also found to have appreciable anticonvulsant activity in scPTZ screen. Two compounds, 3j and 3o, significantly reduced the duration of the immobility time at 25 mg/kg dose, when compared to control.