Natural-Product-Inspired Microwave-Assisted Synthesis of Novel Spirooxindoles as Antileishmanial Agents: Synthesis, Stereochemical Assignment, Bioevaluation, SAR, and Molecular Docking Studies.

Leishmaniasis is a neglected tropical disease, and there is an emerging need for the development of effective drugs to treat it. To identify novel compounds with antileishmanial properties, a novel series of functionalized spiro[indoline-3,2'-pyrrolidin]-2-one/spiro[indoline-3,3'-pyrrolizin]-2-one 23a-f, 24a-f, and 25a-g were prepared from natural-product-inspired pharmaceutically privileged bioactive sub-structures, i.e., isatins 20a-h, various substituted chalcones 21a-f, and 22a-c amino acids, via 1,3-dipolar cycloaddition reactions in MeOH at 80 °C using a microwave-assisted approach. Compared to traditional methods, microwave-assisted synthesis produces higher yields and better quality, and it takes less time. We report here the in vitro antileishmanial activity against Leishmania donovani and SAR studies. The analogues 24a, 24e, 24f, and 25d were found to be the most active compounds of the series and showed IC50 values of 2.43 µM, 0.96 µM, 1.62 µM, and 3.55 µM, respectively, compared to the standard reference drug Amphotericin B (IC50 = 0.060 µM). All compounds were assessed for Leishmania DNA topoisomerase type IB inhibition activity using the standard drug Camptothecin, and 24a, 24e, 24f, and 25d showed potential results. In order to further validate the experimental results and gain a deeper understanding of the binding manner of such compounds, molecular docking studies were also performed. The stereochemistry of the novel functionalized spirooxindole derivatives was confirmed by single-crystal X-ray crystallography studies.

Inductively coupled plasma nanosilica based growth method for enhanced biomass production in marine diatom algae.

This work reports a novel solution-based method to trigger the growth of diatoms for enhanced biomass production, which can efficiently stimulate their applications in nutraceuticals, aquaculture and wastewater remediation. The optimization for the growth of three marine diatoms species was performed using inductively coupled plasma (ICP) synthesized nanosilica which can be a cost-effective and productive method for biomass production. The exponential growth phase was achieved in 14 days with high biomass productivity compared to F/2-Si Media [Chaetoceros sp. (125 ± 3 & 750 ± 3 mgL-1day-1); Skeletonema sp., (185.3 ± 2.63 & 562.5 ± 3.96 mgL-1day-1) and Thalassiosira sp. (312.5 ± 2.51 & 433.5 ± 1.80 mgL-1day-1)] along with a sharp rise of 50-100 fold increment in pigmentation. This work opens up an avenue with novel insights to trigger the growth of diatoms on large scale leading to their better exploitation towards biotechnological applications.

A reversible chromogenic covalent organic polymer for gas sensing applications.

A triazine-cored covalent organic polymer (COP) was designed and synthesized via amine linkages under ambient conditions. The novel architecture of the COP was fully characterized via spectroscopic and analytical techniques. The present COP demonstrates a quick, portable and reversible chromogenic response towards noxious HCl vapours.

Identification of novel indole based heterocycles as selective estrogen receptor modulator.

In the present study, we have designed and synthesized indole derivatives by coalescing the indole nucleus with chromene carbonitrile and dihydropyridine nucleus. Two compounds 5c and 6d were selected from series I and II after sequential combinatorial library generation, docking, absorption, distribution, metabolism and excretion (ADME) filtering, anti-proliferative activity, cytotoxicity, and ER-α competitor assay kit by utilizing estrogen receptor-α (ER-α) dominant T47D BC cells line and PBMCs (Peripheral Blood Mononuclear Cells). Cell imaging experiment suggested that both the compounds successfully cross cellular biomembrane and accumulate in nuclear, cytoplasmic and plasma membrane region. Semiquantitative RT-PCR and Western blotting experiments further supported that both compounds reduced the expression of mRNA and receptor protein of ER-α, thereby preventing downstream transactivation and signaling pathway in T47D cells line. Current findings imply that 5c and 6d represent novel ER-α antagonists and may be used in the development of chemotherapy for the management of BC.