Sustainable and solvent-free synthesis of molecules of pharmaceutical importance by ball milling.

The solvent-free mechanochemical reactions under ball milling have emerged as a promising alternative to traditional solution-based chemistry. This approach not only eliminates the necessity for large quantities of solvents and minimizes waste production, but it also facilitates a unique reaction environment that enables strategies, reactions, and compound syntheses that are typically unattainable in solution. This solvent-less synthetic strategy under ball-milling has been well employed in synthetic organic chemistry in accessing various potential organic molecules including pharmaceutically important molecules and pharmaceuticals or drug-molecules.

A review on new natural and synthetic anti-leishmanial chemotherapeutic agents and current perspective of treatment approaches.

Leishmaniases are considered among the most neglected yet dangerous parasitic diseases worldwide. According to the recent WHO report (Weekly Epidemiological Record, Sep, 2021), 200 countries and territories reported leishmanises cases in 2020; of which 89 (45%) for CL, and 79 (40%) for VL were endemic. Indian subcontinent (India, Bangladesh and Nepal), one of the three eco-epidemiological hotspots of VL, currently reported 18% of the total cases of VL worldwide.

A Composite Recombinant Salivary Proteins Biomarker for Phlebotomus argentipes Provides a Surveillance Tool Postelimination of Visceral Leishmaniasis in India.

Incidence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) has declined by more than 95% since initiation of the elimination program in 2005. As the ISC transitions to the postelimination surveillance phase, an accurate measurement of human-vector contact is needed to assure long-term success. To develop this tool, we identified PagSP02 and PagSP06 from saliva of Phlebotomus argentipes, the vector of Leishmania donovani in the ISC, as immunodominant proteins in humans.

Development of Immunological Assays Based on Antigen for Diagnosis of Canine Visceral Leishmaniasis and Their Multicenter Evaluation in Brazil and Italy.

Canine visceral leishmaniasis (CVL) due to infection is a zoonotic disease prevalent in the areas of South America and the Mediterranean. Infected dogs as reservoirs can contribute to disease transmission and can be a scourge to public health. Therefore, early diagnosis of infected dogs may play a pivotal role in circumscribing disease progression.

Chlorogenic acid acts upon Leishmania donovani arresting cell cycle and modulating cytokines and nitric oxide in vitro.

Aims: Visceral leishmaniasis (VL), caused by Leishmania donovani in India, is fatal if untreated, having serious concern of limited chemotherapeutic options. In this study, we evaluated antileishmanial efficacy of purified chlorogenic acid (CGA) against promastigotes and intracellular amastigotes infected into RAW264.7 macrophages.

A multicentric evaluation of dipstick test for serodiagnosis of visceral leishmaniasis in India, Nepal, Sri Lanka, Brazil, Ethiopia and Spain.

Visceral leishmaniasis (VL) is one of the leading infectious diseases affecting developing countries. Colloidal gold-based diagnostic tests are rapid tools to detect blood/serum antibodies for VL diagnosis. Lack of uniformity in the performance of these tests in different endemic regions is a hurdle in early disease diagnosis.

Discovery of novel quinolinone adenosine A2B antagonists.

A novel series of quinolinone-based adenosine A(2B) receptor antagonists was identified via high throughput screening of an encoded combinatorial compound collection. Synthesis and assay of a series of analogs highlighted essential structural features of the initial hit. Optimization resulted in an A(2B) antagonist (2i) which exhibited potent activity in a cAMP accumulation assay (5.

IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin B in the control of Leishmania donovani infection in India.

Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta.

Immune responses in kala-azar.

Human infection with Leishmania results in diverse clinical and immunopathological situations. The capacity of the parasites to cause this wide range of disease manifestations depends upon their ability to evade the immune defense mechanisms by performing a well-tuned orchestra of hostparasite interactions inside the macrophages. While updated knowledge focus on the key role of cell-mediated immunity (CMI) in protection, the survival strategies of the parasites leads to the suppression of CMI which can further be aggravated by the co-infections with HIV, tuberculosis etc.

Leishmania promastigote membrane antigen-based enzyme-linked immunosorbent assay and immunoblotting for differential diagnosis of Indian post-kala-azar dermal leishmaniasis.

Diagnosis of post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania donovani, is difficult, as the dermal lesions are of several types and resemble those caused by other skin diseases, especially leprosy. Since the disease generally appears very late after the clinical cure of kala-azar in India, it is also difficult to correlate PKDL with a previous exposure to L. donovani.

Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes.

The appearance of phosphatidylserine (PS) on the outer surface of red cells is an important signal for their uptake by macrophages. We report for the first time that procaspase 3 present in the anucleated mature human erythrocyte is activated under oxidative stress induced by t-butylhydroperoxide leading to impairment of the aminophospholipid translocase, PS externalization and increased erythrophagocytosis. This is the first report linking caspase 3 activation to inhibition of flippase activity and uptake of red cells by macrophages.