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Throughout our evolution, the importance of natural products for medicine and health has been increasing and it continues to be a key source of novel anticancer drugs, leads and new chemical entities. Among natural products, tricyclic heteroaromatic alkaloids such as carbazoles are an important class of natural and semi-synthetic organic compounds. In the last few decades medicinal role of natural and semi-synthetic carbazoles has expanded significantly, especially as a vital heterocyclic class of antitumor agents. Some of the carbazoles that displayed potential anticancer activity have undergone clinical trials. However, complications arising due to multidrug resistance in clinical trials led to very few of the selected carbazoles being approved for cancer therapy. Planar, polycyclic and aromatic carbazoles exhibit anticancer activity via DNA intercalation. Further many carbazoles can be cytotoxic by inhibiting DNA-dependent enzymes such as telomerase and topoisomerase I/II.

Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H 37 Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC 50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC 50 = <0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents. KEYWORDS: Antimycobacterial activity, bactericidal, dehydrozingerone, NIAID, thiazole T uberculosis (TB) is a chronic necrotizing bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been a bane of humanity for thousands of years and remains as one of the rampant health problems in the world. TB is an ancient enemy, and current threat that has been ranked among the foremost killers of the 21st century. 1According to a World Health Organization (WHO) report, around 9 million people were found infected and around 1.5 million casualties occurred because of TB. Besides, the life threatening strains of MDR-TB (Multi Drug Resistance Tuberculosis) are appearing, some of which can lead to high mortality rate (e.g., 72−89%) with death occurring in short period (4−16 weeks).2 In 2013 around 480,000 affirmative cases of MDR-TB were witnessed.3 India, China, the Russian Federation, and South Africa have almost 60% of the world's cases of MDR-TB. In addition, the risk becomes even greater if the person is coinfected with the HIV (human immunodeficiency virus). 4 The global resurgence of TB and development of drug resistance necessitates for an imperative attention of medicinal chemists to develop innovative antimycobacterial agents as no new classes of anti-TB agents have been developed since the introduction of rifampin in to clinical practice in 1960s.It is well-known fact that trans-cinnamic acid analogues have recently drawn back the intentness of medicinal chemists due to their admirable pharmacological properties like antioxidant,

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Various substituted carbazolo-thiazoles 6 (a-o) have been synthesized in good yields by molecular hybridization approach. These synthesized compounds were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H 37 Rv strain at National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA. Among the tested series, compound 6c (MIC = 21 µM) exhibited the most promising anti-mycobacterial activity. A brief structure activity relationship (SAR) studies revealed that electron donating groups (OCH 3 and OH) especially on the phenyl ring of thiazole motif exhibited positive correlation with antimycobacterial activity. In addition, they displayed low cytotoxicity against a mammalian Vero cell line using MTT assay, thereby providing a high therapeutic index. This study reveals the significance of molecular hybridization and the scope for the development of carbazole clubbed thiazole compounds as potential anti-mycobacterial agents.

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Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti-HIV, antiviral, anti-inflammatory, anti-Parkinson's and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued.