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Music has occupied our day-to-day life; as it is readily available, accessible and further technological advancement has made access to music a common norm. Music has been present since the very early part of human evolution and has helped in forming society and civilizations. It has served various purposes like social cohesion, emotional expressions, interpersonal communication as well as recreation. Due to its great bonding power; it is important in terms of social dynamics. Music therapy is convenient, inexpensive and user-controlled and seems to be influencing the physiological system positively if rightly used. Vast research is going on to find the right music that could be having a beneficial therapeutic effect. Music seems to affect the pain perception, modulation and also has the affective component to help positively in controlling the pain. This chapter is an attempt to evaluate the various pain modulating effects of music through a systematic music therapy intervention using the vast research work done in this field. This review is consistent to integrate the best scientific evidence for pain relief into practice, education, and research. Music being a non-pharmacologic, nontoxic intervention and is free from adverse effects and also is an inexpensive, low cost modality.

Cancer, which is considered to be the world’s most serious illness cause 8.2 million deaths and this rate may double by 2030. We herein report a new series of 3-(2-(p-substituted)-2-((5-phenyl-1,3,4-thiadiazol-2-yl)imino)-2-(p-substituted)ethylidene)indolin-2-one (15–19) and 5-substituted-5′-substituted phenyl-2′,4′-dihydrospiro[indoline-3,3′-pyrazol]-2-one derivatives (20–24) as potent anticancer agents. These compounds were evaluated for in vitro antitumor activity against the National Cancer Institute panel of 60 cancer cell lines. Among all the synthesized compounds, two compounds 15 and 16 showed remarkable antitumor activity with GI50 (MG-MID) values of 0.65 & 0.72 µM, respectively against Non-small cell lung cancer. To gain insight for mode of binding with Epidermal Growth Factor Receptor kinase enzyme, these compounds were further subjected to docking studies.

This study shows that caspase-1 autocleavage, ASC speck assembly, and mature IL-1β and IL-18 secretion accompany rapid DPP8/DPP9-regulated pyroptosis induction in macrophages expressing a LeTx-responsive Nlrp1b allele., Activating germline mutations in the human inflammasome sensor NLRP1 causes palmoplantar dyskeratosis and susceptibility to Mendelian autoinflammatory diseases. Recent studies have shown that the cytosolic serine dipeptidyl peptidases DPP8 and DPP9 suppress inflammasome activation upstream of NLRP1 and CARD8 in human keratinocytes and peripheral blood mononuclear cells. Moreover, pharmacological inhibition of DPP8/DPP9 protease activity was shown to induce pyroptosis in murine C57BL/6 macrophages without eliciting other inflammasome hallmark responses. Here, we show that DPP8/DPP9 inhibition in macrophages that express a Bacillus anthracis lethal toxin (LeTx)–sensitive Nlrp1b allele triggered significantly accelerated pyroptosis concomitant with caspase-1 maturation, ASC speck assembly, and secretion of mature IL-1β and IL-18. Genetic ablation of ASC prevented DPP8/DPP9 inhibition-induced caspase-1 maturation and partially hampered pyroptosis and inflammasome-dependent cytokine release, whereas deletion of caspase-1 or gasdermin D triggered apoptosis in the absence of IL-1β and IL-18 secretion. In conclusion, blockade of DPP8/DPP9 protease activity triggers rapid pyroptosis and canonical inflammasome hallmarks in primary macrophages that express a LeTx-responsive Nlrp1b allele.

Here a series of 2-butyl-4-chloroimidazole based substituted piperazine-thiosemicarbazone hybrids were designed by combining three different pharmacophoric fragments in single molecular architecture. 2-Butyl-4-chloro-1-(3-(4-substituted)piperazin-1-yl)propyl)-1H-imidazole-5-carbaldehydes (4a-p) prepared by reacting carboxaldehyde 2 with N-alkyl piperazines 3a-p which were condensed with thiosemicarbazine to give desired compounds 5a-p in very good yields. Among all sixteen compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB), two compounds (E)-2-((2-butyl-4-chloro-1-(3-(4-(o-tolyl) piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene)hydrazinecarbothioamide 5e and (E)-2-((2-butyl-4-chloro-1-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-imidazol-5-yl)methylene) hydrazine carbothioamide 5f were found to be the most potent antitubercular agents (MIC: 3.13 μg/mL) with low toxicity profile.

A series of novel 10-substituted 2-hydroxypyrrolobenzodiazepine-5,11-diones designed through structure based rational hybridization approach, synthesized by the cyclodehydration of isotonic anhydride with (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid followed by N-substitution, were evaluated as angiotensin converting enzyme (ACE) inhibitors. Among all the new compounds screened (2R,11aS)-10-((4-bromothiophen-2-yl)methyl)-2-hydroxy-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)dione, 5v (IC₅₀: 0.272 μM) emerged as most active non-carboxylic acid ACE inhibitor with minimal toxicity comparable to clinical drugs Lisinopril, Benazepril and Ramipril. Favorable binding characteristics in docking studies also supported the experimental results.

A series of new β-isatin aldehyde-N,N′-thiocarbohydrazone, bis-β-isatin thiocarbohydrazones, bis-β-isatin carbohydrazones was synthesized by condensation of 5-substituted isatin with thiocarbohydrazide or carbohydrazide. The chemical structures of the newly synthesized compounds were confirmed by FT-IR, 1H NMR, and mass spectral analysis. The synthesized compounds were evaluated for in vitro antiviral activity against various strains of DNA and RNA viruses, but exhibited moderate antiviral activity compared with the reference compounds. Among all the compounds 6c exhibited the highest chemoprevention activity in a two-stage mouse-skin carcinogenesis test. Graphical abstract

A series of novel 2-butyl-4-chloro-1-methylimidazole derived peptidomimetics were designed, synthesized and evaluated for their Angiotensin Converting Enzyme (ACE) inhibitor activity. 2-Butyl-4-chloro-1-methylimidazole-5-carboxylic acid 2 obtained after oxidation of respective carboxaldehyde 1 , was condensed with various amino acid methyl esters 3a – k to give imidazole–amino acid conjugates 4a – k in very good yields. Ester hydrolysis of 4a – k with aqueous LiOH gave the desired peptidomimetics 5a – k . Screening all the new compounds 4a – k and 5a – k using ACE inhibition assay, resulted five compounds 4i , 4k , 5e , 5h and 5i as potent ACE inhibitors with IC 50 of 0.647, 0.531, 1.12, 0.657 and 0.100 μM with minimal toxicity. Among them, 5i emerged as most active ACE inhibitor with greater potency than marketed drugs Lisinopril, Ramipril and relatively equipotent to Benazepril, Quinapril and Enalapril.

A series of novel 1,2,3-triazole-adamantylacetamide hybrids 5a – u , designed by combining bioactive fragments from antitubercular I-A09 and substituted adamantyl urea, were synthesized using copper catalyzed click chemistry. N -(1-Adamantyl)-2-azido acetamide 3 prepared from 1-adamantylamine was reacted with a series of alkyl/aryl acetylenes in the presence of copper sulfate and sodium ascorbate to give new analogues 5a – u in very good yields. Evaluation of all new compounds for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted N -(1-adamantan-1-yl)-2-(4-(phenanthren-2-yl)-1 H -1,2,3-triazol-1-yl)acetamide ( 5t ) as most promising lead MIC: 3.12 μg/mL) with selectivity index >15.

A series of novel 2-(diarylalkyl)aminobenzothiazoles were designed based on commercial synthetic calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors. Which are further modified based on the natural products which are angiotensin converting enzyme (ACE) inhibitors. Completely green protocol was developed for their synthesis. As they are initially designed based on CCBs, they were screened for their ACE inhibition property believing that almost all the compounds will be CCBs. Out of 42 compounds two lead molecules were identified as ACE inhibitors, which were further screened for CCB. As expected both were identified as CCBs with different selectivity over ACE inhibition. Their selectivity over ACE and CCB can be used to treat resistant hypertension.

Molecular hybridization is an emerging structural modification tool to design molecules with better pharmacophoric properties. A series of novel 2-(trifluoromethyl)phenothiazine-1,2,3-triazoles 5a–v designed by hybridizing two antitubercular drugs trifluoperazine and I-A09 in a single molecular architecture, were synthesized in very good yields using click chemistry. Among the all ‘22’ compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb), three analogs 5c, 5l and 5o were found to be most potent (MIC: 6.25 μg/mL) antitubercular agents with good selectivity index.

Music has occupied our day-to-day life; as it is readily available, accessible and further technological advancement has made access to music a common norm. Music has been present since the very early part of human evolution and has helped in forming society and civilizations. It has served various purposes like social cohesion, emotional expressions, interpersonal communication as well as recreation. Due to its great bonding power; it is important in terms of social dynamics. Music therapy is convenient, inexpensive and user-controlled and seems to be influencing the physiological system positively if rightly used. Vast research is going on to find the right music that could be having a beneficial therapeutic effect. Music seems to affect the pain perception, modulation and also has the affective component to help positively in controlling the pain. This chapter is an attempt to evaluate the various pain modulating effects of music through a systematic music therapy intervention using the vast research work done in this field. This review is consistent to integrate the best scientific evidence for pain relief into practice, education, and research. Music being a non-pharmacologic, nontoxic intervention and is free from adverse effects and also is an inexpensive, low cost modality.