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A mild and efficient protocol was developed for the synthesis of pyrazole and 2°-amine hybrid conjugates through an InCl3 Ugi four-component reaction followed by a base mediated secondary amine coupling reaction. MCRs have been used extensively in the field of combinatorial chemistry, which offers the synthesis of libraries of similar molecules in a parallel fashion. A small library of novel N-allyl-N-(1-(4-(aminomethyl) phenyl)-2-(tert-butylamino)-2-oxoethyl)-1,3-diphenyl-1H-pyrazole-4-carboxamide scaffold was designed and synthesized through a one-pot four-component Ugi reaction, the resulting Ugi product pyrazole derivative coupled with various secondary amines to prepare target pyrazole – amine conjugate molecules. The structures of synthesized conjugates confirmed by spectroscopic techniques (NMR, C, H, N analysis, and MS). The in vitro antimicrobial survey of these pyrazole-secondary amine conjugates was supported by DFT studies; thereby notifies the conjugates are promising antimicrobial agents and are comparable to the standard antimicrobial molecules such as ampicilin, griseofulvin, isoniazide and rifampicin.

Vitamin-K is a demanding multi-functional health product in the market and belongs to a class of isoprenoid molecules that comprises methylnaphthoquinone (MK) unit attached to an isoprene side chain. They are fat soluble and differ in the extent of side chain & obtained in the nature as vitamin K1 (phylloquinone), menaquinone/vitamin K2, and other lipoquinones. Owing to their owned polyprenyl side chain, they are hydrophobic/lipophilic in nature. Generally, the synthesis of vitamin K and its variants suffers with isomerization (for example 11 isomers were identified for cis/trans MK-7). Naturally, in bio-systems vitamin K produces through shikimic acid pathway and terpene biosynthetic pathway for the synthesis of menaquinone part & prenyl side chain parts respectively. Menadione or its auxiliaries are commonly being used as substrates to the synthesis of vitamin K variants through the involvement of condensation reactions, Friedel-Craft alkylation’s, Claisen rearrangement, Diels-Alder reactions and others. Importantly, organometallic reagents, such as Grignard, Gilman, organotelluride and other reagents could be the promising and consistent choice of substrate to the synthesis of various vitamin K’s. Vitamin K is well known for blood coagulation. As an antihaemorrhagic vitamin, it’s also being the current interest for the treatment of bone and vascular diseases. In addition, vitamin k is indispensable for the activation of vitamin K dependent (VKD) proteins and that are present almost in all tissues and responsible for hemostasis, bone mineralization, arterial calcification, apoptosis, phagocytosis, growth control, chemotaxis, and signal transduction. This chapter summarizes various synthetic approaches of vitamin K & derivatives and their biological functions.

With the aim to discover potent and novel antitumor agents, a series of thiourea compounds bearing 3-(4-methoxyphenyl)azetidine moiety were designed according to the essential pharmacophoric features of the reported VEGFR-2 inhibitors and synthesized. All the synthesized compounds were evaluated for their in vitro anticancer activity against various human cancer cell lines (lung (A549), prostate (PC3), breast (MCF-7), liver (HepG2), colon (HCT-116), ovarian (SKOV-3), skin (A431), brain (U251) and kidney (786-O)). 3-(4-Methoxy-3-(2-methoxypyridin-4-yl)phenyl)-N-(4-methoxyphenyl)azetidine-1-carbothioamide (3B) was found to be most potent member against PC3, U251, A431, and 786-O cancer cell lines with EC50 values 0.25, 0.6, 0.03, and 0.03 µM, respectively and showed more potency than Doxorubicin in PC3, A431, and 786-O cell lines. Compounds 1B to 7B showed EC50 values ranging from 0.03 to 12.55 µM in A431 cell line. Compound 3-(4-methoxy-3-(pyridin-4-yl)phenyl)-N-(4-methoxyphenyl)azetidine-1-carbothioamide (1B) was found to be highly efficient in A431 and 786-O cell line with EC50 values of 0.77 and 0.73 µM respectively. All the compounds exhibited good to moderate cytotoxic activity. The pharmacophoric features and molecular docking studies confirmed the potentialities of compounds 1B, 2B, 3B and 5B to be VEGFR-2 inhibitors. Moreover, in silico ADMET prediction indicated that most of the synthesized compounds have drug-like properties, possess low adverse effects and toxicity. In addition, the DFT studies for the most active compounds (1B and 3B) were carried out. In the end, our studies revealed that the compounds 1B and 3B represent promising anticancer potentialities through their VEGFR-2 inhibition.

Department of Chemistry, Uka Tarsadia University, Bardoli, Surat-394 350, Gujarat, India E-mail: satyamssd@gmail.com Medicinal Chemistry Department, Indian Institute of Integrative Medicine, Canal Road, Jammu-180 001, Jammu & Kashmir, India Bioorganic and Med. Chemistry Lab, School of Chemistry and Chemical Engineering, Southwest University, Chongqing-400715, China Manuscript received online 16 September 2019, revised 17 september 2019, accepted 18 September 2019 The utility of oxone has been extended to an efficient aromatizing agent and successfully applied to the aromatization of tetrahydro-β-carbolines under mild conditions, to produce aromatized β-carboline esters and amides. It is expediently applicable to all kinds of C-1 subsisted (aryl, alkyl, and acyl) tetrahydro-β-carboline esters. It also gives a direct and productive one-pot conversion of tetrahydro-β-carbolines ester to aromatized β-carboline amide. Further, the application of this method finds an easier route to the synthesis of marinacarbolines A and C.