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Innumerable studies associated with cellular differentiation, tissue response and disease modeling have been conducted in two-dimensional (2D) culture systems or animal models. This has been invaluable in deciphering the normal and disease states in cell biology; the key shortcomings of it being suitability for translational or clinical correlations. The past decade has seen several major advances in organoid culture technologies and this has enhanced our understanding of mimicking organ reconstruction. The term organoid has generally been used to describe cellular aggregates derived from primary tissues or stem cells that can self-organize into organotypic structures. Organoids mimic the cellular microenvironment of tissues better than 2D cell culture systems and represent the tissue physiology. Human organoids of brain, thyroid, gastrointestinal, lung, cardiac, liver, pancreatic and kidney have been established from various diseases, healthy tissues and from pluripotent stem cells (PSCs). Advances in patient-derived organoid culture further provides a unique perspective from which treatment modalities can be personalized. In this review article, we have discussed the current strategies for establishing various types of organoids of ectodermal, endodermal and mesodermal origin. We have also discussed their applications in modeling human health and diseases (such as cancer, genetic, neurodegenerative and infectious diseases), applications in regenerative medicine and evolutionary studies.

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Reaction o f 4-hydroxy-3-prenylquinolin-2(l H)one (5 a) with iodine and silver acetate gave a iodopyranoquinoline (6 a), which was then converted into the alkaloids khaplofoline (1) and ribalinine (2). Reaction o f 5 a with iodine and mercuric oxide afforded a mixture o f 6a and its angular isomer 7 a; the coversion o f latter into flindersine (10) is described.Pyranoquinoline alkaloids, which possess inter esting pharmacological properties are known [1,2] to occur in the plant family Rutaceae. The alka loids, khaplofoline (1) and ribalinine (2), isolated respectively from Haplophyllum foliosum (Vved) [3] and Balfourodendron riedelianum [4], members of the rutaceae, are structurally proven to be of pyrano [2,3-b]quinoline systems. Several reports have appeared in the literature for the synthesis of 1 [3,5-9] and 2 [10-12], but the yields of 1 and 2 in these attem pts were not quite appreciable and are often attended by the form ation of their isomeric products. 0 R2 1: R1 = R2 = H 2 : R1 = CH3; R2 = OH I R1In this com m unication, we wish to present an al ternative but elegant methodology for deriving the titled alkaloids from 5, which in turn was prepared [13] from 4-hydroxyquinolin-2(l H)one 3. Reac tion of 5 a with iodine, in the presence of silver ace tate in glacial acetic acid at room tem perature gave a single product (m .p. 176-177 °C) in 80% yield. It was identified to be 3-iodo-3,4-dihydro-5-oxo-2,2-dimethyl-2H-pyrano[2,3-b]quionoline (6a). In its IR spectrum two bands at 3420 cm " 1 and 1620 cm -1 were ascribable to a N H stretching and a 4-quinolinone [14] moiety respectively. In its 'H N M R spectrum; the six proton singlet at S 1.58 ppm was characteristic of a gem-dimethyl group, two double doublets with J = 17.4 and 6.6 Hz and * Reprint requests to Dr. K. J. Rajendra Prasad.Verlag der Zeitschrift für Naturforschung. D-W -7400 Tübingen 0 9 3 2 -0 7 7 6 /9 2 /0 7 0 0 -1 0 1 6 /$ 01.00/0 a single proton triplet at S 4.68 ppm were ascriba ble to methylene and methine protons forming ABX system and a singlet at ö 11.83 ppm assigna ble to N H proton. The molecular ion peak (M +) at mle: 355 (55%) in its mass spectrum and elemental analysis C 47.30, H 4.05 and I 35.80% are well agreed to the molecular formula C 14H 14N 0 2I. Thus we realized the preparation of iodopyrano quinoline in high yield and it has proven to be a utility in heterocyclic synthesis. 6 a on alkaline hy drolysis using 0. 1% aqueous sodium hydroxide yielded 3-hydroxykhaplofoline (8); which on heat ing with methyl iodide furnished the alkaloid ribal inine 2 [4] in 90% yield. W ith the view to adducing further attestation of the iodopyranoquinoline structure assigned for the product 6 a, it was dehydroiodinated by refluxing in pyridine to chromenoquinoline 9. F urther reduction of 9 with H 2, P d -C (5 )% gave the alkaloid khaplofoline (1), which was confirmed with authentic sample [3] (m.p. CoTLC, undepressed m.m.p., superimposable IR spectra) (Scheme 1).Similar treatm ent when extended to 6-methyl-4-hydroxy-3-prenylquinolin-2(l H)one (5...

Polyphosphoric acid (PPA)-catalyzed cyclization of 2-ono-3-vinylquinolinecarboxylic acid (1) yielded 3,4-dihydro-2,2-dimethyl-2H-pyrano[2,3-b]quinoline (4). The same reaction of 4-methoxy-2-oxo-3-vinylquinolinecarboxylic acid (1g) afforded 4-methoxy-2,2-dimethylpyrano[2,3-b]quinoline (4g), which on hydrolysis with ethanolic hydrochloric acid gave khaplofoline (5). The Prevost reaction of 4-methoxy-3-prenylquinolin-2-one (6) using I2/HgO in acetic acid yielded 4-methoxy-2-isopropylfuro[2,3-b]quinoline (7). Compound 7 on reduction with H2/Pd-C followed by N-methylation and de-O-methylation afforded lunacrine (10a). A similar reaction sequence on 6b gave demethoxylunacrine (10b).

The ent kaurene diterpenoid, melissoidesin was isolated from the acetone extract of the leaves of Isodon wightii and the structure was designated as 3beta, 11beta, 15beta-trihydroxy-6alpha-acetoxy-ent-kaur-16-ene based on spectral data and previous reports. Melissoidesin isolated from the acetone extract of leaves showed potent antiacetylcholinesterase activity and the IC(50) value was observed as 215 microg mL(-1). DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging activity of melissoidesin was significant and the IC(50) value was 138 microg mL(-1). The significant reducing property of the melissoidesin was stronger in high concentration. IC(50) value of melissoidesin on hydroxyl radicals and metal chelation was observed as 99 and 143 microg mL(-1), respectively. The 50% inhibitory concentration of melissoidesin on lipid peroxidation was calculated as 133 microg mL(-1). These findings indicate that ent kaurene diterpenoid, melissoidesin was promising antiacetylcholinesterase and antioxidant which can be used as food and drug preparations.