Pramod P. Kattimani

Synthesis, characterization and in vitro anticancer evaluation of novel 1,2,4-triazolin-3-one derivatives

A series of novel 2-(4-chlorophenyl)-5-methyl-4-(2-amine/oxy-ethyl)-2,4-dihydro-[1,2,4]triazol-3-one (5a-t) were synthesized and in vitro anticancerous action of the resulting compounds was studied against NCI-60 Human Tumor Cell Line at a single high dose (10(-5) M) concentration for primary cytotoxicity assay. Among the tested compounds (5a-e, 5g-h, 5k, 5p), the compound 5g (NSC: 761736/1) was further evaluated for five dose criteria at five different minimal concentrations against the full panel of 60 human tumor cell lines which exhibited activity against Leukemia (GI50: 1.10 μM), Non-Small Cell Lung Cancer (GI50: 1.00 μM), Renal Cancer (GI50: 1.00 μM), Colon Cancer (GI50: 1.66 μM), CNS Cancer (GI50: 1.36 μM), Melanoma (GI50: 1.82 μM), Ovarian Cancer (GI50: 1.64 μM) and Breast Cancer (GI50: 1.69 μM).

Expedient synthesis of benzimidazoles using amides

In the present report an efficient, rapid, facile and inexpensive route for the synthesis of benzimidazoles using 1,2-arylenediamines and N,N-dimethylformamide in acidic medium under thermal/microwave condition is developed. This reaction was further explored with the different amides to afford a library of 2-substituted benzimidazoles. The advantage of the present synthetic method includes shorter reaction time, easy work up and excellent yields without using catalysts.

Synthesis of novel imidazo[2,1-b][1,3,4]thiadiazoles appended to sydnone as anticancer agents

A novel series of 3-aryl-4{6′-(6′′-substituted-coumarin-3′′-yl) imidazo[2,1-b][1,3,4]thiadiazol-2′-yl}-sydnones 5h–5s were synthesized and screened for their anticancer and DNA cleavage activities and analyzed for pharmacological parameters such as toxicity, drug-likeliness, and drug score for oral bioavailability. In vitro toxicity assay was carried out by assessing the survival E. coli AB1157 (wild type) cultures. Some of the compounds have shown significant anticancer activities also.

Synthetic utility of sydnones: synthesis of pyrazolines derivatized with 1,2,4-triazoles as antihyperglymic, antioxidant agents and their DNA cleavage study

Ring transformation of sydnone (1a–i) to 1,3,4-oxadiazoline-2-one (2a–i) was carried out using bromine in acetic anhydride. The compounds (2a–i) on heating with hydrazine hydrate gave 1,2,4-triazole (3a–i) in good yields. The structure of these unknown compounds was confirmed by IR, 1H NMR, MS and elemental analysis. Further, these compounds were evaluated for the extent of penetration into biological membranes (clogP) drug likeliness and finally drug score was calculated. The title compounds were also screened for their antihyperglycemic, DNA cleavage and antioxidant activity.

Synthesis of Sydnone Substituted Biginelli Derivatives as Hyaluronidase Inhibitors

A novel series of Biginelli 2–3 (a and b) and Biginelli‐like compounds 4–7 (a and b) were synthesized from 3‐aryl‐4‐formylsydnone 1 (a and b). Since the crystal structure of hyaluronidase was unavailable, the human hyaluronidase protein structure was used as template and homology modeling was performed, validated by Ramachandran plots and subjected to docking studies along with in vitro anti‐inflammatory activity assessment against hyaluronidase. Compounds 2–3 (a and b) exhibited potent enzyme inhibition.

An expeditious synthesis of 1,2,4-triazolinones appended to 1,3-thiazoles using zinc triflate as catalyst

A convenient and high yielding method was developed for the ring transformation of 1,3,4-oxadiazolinones (2a-e) from 3-arylsydnones (1a-e) to 1,2,4-triazolinones (3a-e) using zinc triflate as catalyst and then appended to 1,3-thiazoles via an imino bridge in one-pot reaction with excellent yields. The novel compounds were further scored for c logP values, drug likeliness, drug score and toxicity rates using molecular OSIRIS property explorer. Selective compounds were also screened for antimicrobial studies.

Design, synthesis, docking and in vitro antifungal study of 1,2,4-triazole hybrids of 2-(aryloxy)quinolines

Abstract Substituted quinolines containing a 1,2,4-triazole moiety were synthesized using reported methods. The molecular docking studies support the experimental results that these compounds are active against A. fumigatus and C. albicans where N-myristoyl transferase (NMT) and dihydrofolate reductase (DHFR), respectively, are the target enzymes. The analogues that contain methoxy and chloro substituents exhibit the best antifungal activity.

1-(4-Chloro­phen­yl)-1H-1,2,4-triazol-5(4H)-one

In the title compound, C8H6ClN3O, the dihedral angle between the 1,2,4-triazole and benzene rings is 4.60 (9)° and an intramolecular C—H⋯O interaction closes an S(6) ring. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) loops and C—H⋯O interactions link the dimers into [100] chains. Weak π–π stacking interactions [centroid–centroid distance = 3.644 (1) Å] are also observed.