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A new series of 1,2,3-triazole linked mercaptobenzoxazole/oxazolo- [4,5-b] pyridine-2-thiol derivatives (6a-j) were synthesized starting from 2-aminophenol/2-aminopyridin-3-ol in three steps via cyclization, alkylation followed by reaction with various aromatic azides using click chemistry approach. All the synthesized compounds were evaluated for their antimicrobial activity viz. E. coli, P. aeruginosa, S. aureus and S. pyogenus and three pathogenic fungi viz. C. albicans, A. niger and A. clavatus and promising compounds were identified.

Cancer is a major health problem and the most upsetting disease in humans, leading to death in both developed and developing countries. Proper treatment of the disease is still a challenge. Chemotherapy is considered one of the regimens to cure this disease. In this study, a series of 1,2,3-triazole and isoxazole-linked benzothiazole/benzoxazole derivatives were synthesized and evaluated for their anticancer activity against human cancer cell lines, such as HeLa (cervical), and A549 (lung) cell lines, with HEK-293 cell line used as a control. Among them, conjugates 8a, 8f, 13g, 13h and 13j displayed significant cytotoxic activity against human cancer cell lines. Furthermore, these active conjugates induced an increase in the expression of key apoptotic genes that are involved in the intrinsic pathway of apoptosis such as caspase-9, caspase-3, BAX and cytochrome-c. This study may provide possible anti-cancer therapeutics against HeLa and lung cancer cells.

In the past few decades, heterocyclic compounds and their derivatives have gained popularity due to their prominent medicinal importance. The versatile and synthetically accessible 2-aminobenzothiazole scaffolds are quite fascinating for multiple applications in both synthetic organic chemistry and biological fields due to their potent pharmacological activities. A large number of efforts have been made to develop a wide range of methodologies for the synthesis of 2-aminobenzothiazole and its derivatives. Moreover, 2-aminobenzothiazole significantly serves as a reactant or a reaction intermediate for affording various fused heterocycles since NH2 and endocyclic N functions of 2-aminobenzothiazole are suitable to assist reactions with common bis electrophilic reagents to form a diverse fused heterocyclic scaffold. This review highlights various synthetic methodologies and chemical reactions of 2-aminobenzothiazole.

A new series of 2-imino-4-thiazolidinone derivatives (7a–7t) has been synthesised and screened for their cytotoxicity against three cancer cell lines (B16F10, A549, PANC-1) and normal cell line (CHO). Among the compounds tested, compounds 7k, 7m, 7n showed potent cytotoxicity against B16F10 cell line with IC50 between 3.4 and 7 μM. Interestingly these three compounds are non toxic to non cancerous CHO cells and induced apoptosis in B16F10 cells observed by DNA damage analysis through PI/Hoechst double staining method. Compounds 7k and 7n induced G0/G1 cell cycle arrest while compound 7m induced G2/M cell cycle arrest in B16F10 cells which confirms that these compounds have role in cancer cell cycle regulation. Additionally, compound 7m showed generation of intracellular reactive oxygen species (ROS) in B16F10 cells that may contribute in the cell cycle arrest whereas compounds 7k and 7n show anti-cancer activity through independent of ROS formation. Induction of apoptosis, cell cycle arrest in B16F10 cells are found to be the anti-cancer mechanism of these three compounds. The results all together demonstrate the potent cytotoxic nature of these compounds in cancer cells could be considered as new class of chemotherapeutic agents in near future.

A series of novel triazole linked N-(pyrimidin-2yl)benzo[d]thiazol-2-amine 5a-k were synthesized and evaluated for anticancer activity against breast (MCF-7), lung (A549) and skin (A375) cancer cell lines and their cytotoxic effects were compared against normal breast epithelial cells. The effect of compounds on cell cycle of MCF-7 breast cancer cell line was investigated by FACS. Result indicated G2/M cell cycle arrest of MCF-7 cells. Further promising compounds 5b, 5g, 5h and 5i were tested for their apoptosis inducing ability as well as inhibitory activity against key proteins NF-kB, Survivin, CYP1A1, and ERK1/2 which help in cancer cell survival and proliferation. The apoptotic aspect of these compounds is further evidenced by increase in the activity of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in highly malignant breast cancers and can be selected for further biological studies.

A facile multicomponent synthesis of desirable medicinal scaffolds based on thiazoline, thiazolidinone and thiazolidinol derivatives has been disclosed. The synthesis employs the reaction of a primary amine and carbon disulphide in a microwave, to generate a symmetrical thiourea in situ. The subsequent addition of e.g. 3-bromo-1,1,1-trifluoropropan-2-one affords the desired product, in an efficient one-pot process.

A new series of fluoro 1,2,3-triazole tagged amino bis (benzothiazole) derivatives 8, 9 were prepared starting from 2-amino benzothiazole in four steps via amination, cyclization, alkylation followed by reaction with various azides under sharpless conditions through click chemistry approach. All newly synthesized compounds were screened for their antimicrobial and cytotoxic activity against four human cancer cell lines (U937, THP-1, Colo205, and A549), and promising compounds have been identified.

A practical and efficient protocol has been developed for the synthesis of 2-imino-4-thiazolidinone through a unique one pot three-component reaction of variety of amines, isothiocyanate and ethylbromoacetate in water. The method is free of catalyst and other toxic solvents, has shorter reaction times, high-yielding, effortlessness in isolation of product, making it more eco-friendly process, and suitable for large scale operation.

A series of isoxazole derivatives of 6-fluoro-N-(6-methoxybenzo[d]thiazol-2-yl)benzo[d]thiazol-2-amine and N-(pyrimidin-2-yl)benzo[d]thiazol-2-amine were synthesized and evaluated for their cytotoxicity. These compounds exhibited anti-cancer activity against Colo205, U937, MCF7 and A549 cancer cell lines and were more effective against the Colo205 cell line, with IC50 values ranging from 5.04–13 μM, than against other cell lines. The detailed effects of one of the promising compounds, 20c, on the biological properties of the Colo205 cell line were studied. Interestingly, compound 20c induced G2/M cell cycle arrest. The levels of p53 increased tremendously in 20c-treated Colo205 cells. The balance in levels of key mitochondrial proteins such as Bcl-2 and Bax was altered, which resulted in apoptosis by accelerating the expression of caspases. Thus, compound 20c can be considered as a potential small-molecule activator of p53, which regulates the equilibrium between rapid cell proliferation and apoptosis, and can be considered as a potential plausible candidate for further biological testing in in vivo colon cancer models.

Benzothiazolyl carbaimides (III) and (VI) are obtained from aminobenzothiazoles (I) and (V) and isothiocyanates (II) by a novel method using DMAP as a catalyst.

A new series of Mannich bases of 2-arylimidazo[2,1- b ]benzothiazoles were synthesized and evaluated for their anti-cancer activity. These compounds showed better cytotoxicity activity with IC 50 values ranging from 2.8 to 8.0 μM in HepG2, MCF-7 and HeLa cell lines. Further mechanism aspects responsible for the anti-cancer activity of two promising compounds 3c and 3f in HepG2 cell line were studied. Interestingly, 3c , 3f induced G2/M cell cycle arrest with down regulation of cyclin B and up regulation of Chk2 protein. Moreover, compounds 3c , 3f also showed the characteristic features of apoptosis such as enhancement in the levels of caspase-3. Treatments with compounds led to a decrease in levels of vital cell proliferation proteins such as Jun (C-Jun, JunB), p38 MAPK, p-JNK and PKCα. The compound 3f of the series could be considered as the potential lead for its development as a novel anti-cancer agent.

A facile multicomponent synthesis of desirable medicinal scaffolds based on thiazoline, thiazolidinone and thiazolidinol derivatives has been disclosed. The synthesis employs the reaction of a primary amine and carbon disulphide in a microwave, to generate a symmetrical thiourea in situ. The subsequent addition of e.g. 3-bromo-1,1,1-trifluoropropan-2-one affords the desired product, in an efficient one-pot process.

A highly, efficient synthetic protocol for the synthesis of 2-aminooxazolo[4,5- b ]pyridine derivatives is established via intramolecular C–O bond coupling using copper iodide as a catalyst and water as solvent. A variety of functionalized substrates were found to react under this reaction conditions to provide products in good to excellent yields.

A practical and efficient protocol has been developed for the synthesis of 2-imino-4-thiazolidinone through a unique one pot three-component reaction of variety of amines, isothiocyanate and ethylbromoacetate in water. The method is free of catalyst and other toxic solvents, has shorter reaction times, high-yielding, effortlessness in isolation of product, making it more eco-friendly process, and suitable for large scale operation.

A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM.

A highly, efficient synthetic protocol for the synthesis of 2-aminooxazolo[4,5- b ]pyridine derivatives is established via intramolecular C–O bond coupling using copper iodide as a catalyst and water as solvent. A variety of functionalized substrates were found to react under this reaction conditions to provide products in good to excellent yields.

New series of isoxazoles (III) and triazoles (V) are synthesized and evaluated for their anticancer activity against three cancer cell lines.

Benzothiazolyl carbaimides (III) and (VI) are obtained from aminobenzothiazoles (I) and (V) and isothiocyanates (II) by a novel method using DMAP as a catalyst.

A new series of isoxazoles and triazoles linked 2-phenyl benzothiazole were synthesized and evaluated for their anticancer activity. These compounds have been tested for their cytotoxicity three cancer cell lines. Among the compounds tested, compound 5d showed good cytotoxicity against Colo-205 and A549 cells in comparison to standard control PMX 610(1). Further compound 5d has been tested for its apoptotic activity and its inhibitory activity against caspase and PARP proteins. Hence this compound has the potential that it can be selected for further biological studies.

Benzothiazolyl thiocarbamides has been achieved using a catalytic amount of 4-dimethylaminopyridine (DMAP) followed by its chemoselective oxidative cyclization with 1,3-di-n-butylimidazolium tribromide[bbim][Br(3)] to afford the N-bis-benzothiazole derivatives. All the synthesized compounds were evaluated for cytotoxic activity against two human monocytic cell lines (U 937, THP-1) and a mouse melanoma cell line (B16-F10). Based on their IC(50) values, the majority of the benzothiazolyl thiocarbamides and N-bis-benzothiazoles had significant antiproliferative activity on U 937 and B16-F10 cells, the compounds 3b, 3e, 3f, 3k, 6c and 6h were found to be the most active. The present findings indicate clearly that the compound 3e exhibited more antiproliferative activity on U 937 cells than the standard molecule, etoposide. Nevertheless, these compounds have shown comparatively less cytotoxicity towards THP-1 cells.

Correction for “Fluorinated thiazolidinols cause cell death in A549 lung cancer cells via PI3K/AKT/mTOR and MAPK/ERK signalling pathways” by Ravindra M. Kumbhare et al., Med. Chem. Commun., 2016, DOI: 10.1039/c5md00603a.